The Medical "Benefits" of Smoking Marijuana (Cannabis): a Review of the Current Scientific

Literature

by Rich Deem

Introduction

Marijuana Harmless?

In 1997, the British newspaper The Independent began a campaign to decriminalize marijuana
use, describing it as a relatively harmless drug, eventually leading to the British Government
downgrading the legal status of the drug. Ten years later, the same newspaper published
another article entitled "Cannabis: an apology," reversing its campaign for marijuana
decriminalization because, there is increasing evidence that marijuana use is far from harmless.

Rich Deem

Marijuana (cannabis) is the most widely used illegal drug in many developed countries.1 Medical
studies have shown that the active ingredient in marijuana, delta-9-tetrahydrocannabinol (THC),
might provide some medical benefits in some patients. Under the impression that these benefits
were substantial, voters in California and Arizona approved initiatives allowing the use of
"medical" marijuana by patients under certain circumstances. This paper represents a current
review of the medical literature regarding the benefits and drawbacks of using marijuana for
medical or recreational purposes. A companion paper examines the moral and biblical questions
about the Christian's use of marijuana.

THC mode of action

THC StructureTHC Structure

THC is a cannabinoid compound, which binds to CB1 cannabinoid receptors in the human brain.2
These cannabinoids mimic naturally occurring endocannabinoids produced within the brain, but
with more powerful effects. CB1 receptors are found in the cerebral cortex (primarily the frontal
regions), the basal ganglia, the cerebellum, the hypothalamus, the anterior cingulate cortex, and
the hippocampus.3 The effects of THC have been experimentally shown through the use of
animal studies and some in vitro human studies. THC acts by inhibiting the release of
neurotransmitters, including L-glutamate, GABA, noradrenaline, dopamine, 5-HT and
acetylcholine. Although endocannabinoids are rapidly inactivated by the enzyme fatty acid
amide hydrolase, exogenous cannabinoids, such as THC, persist for extended periods of time,
resulting in the noted physiological effects.
Medical benefits of marijuana

Anecdotal evidence for the beneficial effects of marijuana eventually led to the design of
controlled scientific studies to examine the benefits of marijuana compared to other treatments.
A 1997 review of 6059 marijuana-related articles in the medical literature revealed 194 titles on
antiemetic properties, 56 on glaucoma, 10 on multiple sclerosis, 23 on appetite, and 11 on
palliative or terminal care.2 Numerous studies have been performed since that time, with most
concentrating on the analgesic properties of cannabis and its derivatives.

Antiemetic (anti-nausea) use

Early on, THC had been shown to be effective for some patients who suffered nausea from
cancer chemotherapy treatments. However, the narrow window between the anti-emetic dose
and that which caused unwanted psychic effects made THC difficult to use.3 In some studies,
negative side effects occurred in up to 81% of patients.4 In one of the few studies using smoked
marijuana, 20% of patients dropped out of the study, while another 22% reported no relief of
nausea symptoms.5 The advent of serotonin 5-HT3 receptor antagonists as new and more
powerful anti-emetic drugs that were free of unwanted psychic effects has made cannabinoid
use less attractive. For this reason, physicians virtually never prescribe marijuana or THC as an
antiemetic for use by chemotherapy patients.6

Multiple sclerosis

Studies have shown that cannabis can relieve muscle pain and spasticity in patients suffering
from multiple sclerosis7 and can control tremors in multiple sclerosis animal models.8 However,
a study in ten patients with spastic multiple sclerosis showed that smoking marijuana further
impaired posture and balance in those patients.9 In addition, MS patients who used marijuana
had a greater number of psychiatric diagnoses and a slower mean performance time on standard
neurological tests.10 Some randomized, double-blind, placebo-controlled, parallel group
crossover trials have found no significant improvement of MS symptoms during cannabis plant
extract use. However, in some trials patients did show an increase in aggressive behavior and
paranoiac tendencies in a standard psychological test.11 Another placebo-controlled study,
examining the effect of a cannabis extract on spasticity in MS, found a positive partial relief of
symptoms in 40% of patients.12 A 10-week, placebo-controlled study of MS patients found that
42% withdrew due to lack of efficacy, adverse events and other reasons. Patients reported 292
unwanted effects, of which 251 were mild to moderate, including oral pain, dizziness, diarrhea,
nausea. Three patients suffered five serious adverse events, including two seizures, one fall, one
aspiration pneumonia, one gastroenteritis. Four patients had first-ever seizures. A minority of
patients received some relief of symptoms.13 So, overall, studies show that a minority of
multiple sclerosis patients can receive some symptom relief through the use of marijuana
extracts or THC, although a significant percentage of patients suffer unwanted adverse effects.

Glaucoma

THC has been shown to reduce intraocular pressure in laboratory animals and humans who have
glaucoma.14 However, it was found that intraocular pressure was reduced only when patients
stayed under the effects of THC almost continuously.15 Since the early studies, more effective
medications, such as 13-blockers and prostaglandins, have been developed to control intraocular
pressure. Obviously, glaucoma medications that don't require one to be continuously high are
preferable to those that have unwanted side effects.

Appetite

Regular marijuana users are aware of the phenomenon known as the "munchies." Laboratory
studies have shown that THC does increase the appetite (not a good thing for most of us).16
However, for those suffering from debilitating diseases, such as AIDS-related wasting syndrome,
THC has been shown to be effective in maintaining body weight.17

Analgesia (pain relief)

Some clinical studies have indicated that THC has some analgesic activity in patients with
cancer.18 However, there is a narrow therapeutic window between doses that produce useful
analgesia and those that produce unacceptable central nervous system effects. Several studies
have shown improvement of pain at higher doses,19 while others have shown no effect or a
negative effect at higher doses compared with placebo.20

Medical marijuana summary

The use of marijuana or cannabis extracts for medical treatment has been extensively studied
over the last 20 years. Initial enthusiasm for THC as an antiemetic or to reduce intraocular
pressure has waned with the advent of new medications that provide superior medical benefits
with fewer adverse effects. The main success of THC has been found in patients suffering from
AIDS-related wasting syndrome and in some cases in which patients are suffering from
intractable pain. However, nearly all of these studies involved the use of controlled doses of
purified cannabinoids, bypassing the adverse effects associated with smoking marijuana. Dr.
Robert L. DuPont, Georgetown University School of Medicine, says that most opponents of the
medical use of smoked marijuana are not hostile to the medical use of THC, while "most
supporters of smoked marijuana are hostile to the use of purified chemicals from marijuana,
insisting that only smoked marijuana leaves be used as 'medicine,' revealing clearly that their
motivation is not scientific medicine but the back door legalization of marijuana."21

Detrimental effects of marijuana

Studies examining the efficacy of "medical" marijuana have found that a significant percentage
of patients suffer from some form of adverse side effects. However, these studies have been
limited to a duration of a few weeks to months. Another series of studies have examined the
long-term effects of recreational marijuana use.

Dosage Problems

One of the main problems with the use of crude "medical" marijuana is that the amount of THC
in the preparations varies up to 10-fold, depending upon if the marijuana is made from the
flowers or the whole plant.22 Those who can afford the "good stuff" usually get a substantially
higher dose of THC than those who buy the "cheap stuff." In addition, studies demonstrate a
trend for increasing concentration of THC over the last ten years.23 Because of dosage problems,
crude marijuana as a medical "treatment" has proved problematic, despite California's assertion
that there is such a thing as "medical" marijuana.

Brain effects

Cannabis & BrainCannabis & Brain

A recent study using an MRI technique, diffusion tensor imaging, mapped the structural integrity
of brain tissue in eleven heavy marijuana users and eleven age matched controls. The study
found impaired structural integrity affecting the fibre tracts of the corpus callosum, suggesting
the possibility that the structural abnormalities in the brain may underlie cognitive and
behavioral consequences of long-term heavy marijuana use.24 Another MRI study found that
heavy cannabis users had an averaged 12 per cent volume reduction of the hippocampus, and a
7 per cent reduction of the amygdala compared to controls (see image to right).25 In addition,
the study found that long-term cannabis users suffered from psychotic experiences, such as
persecutory beliefs and social withdrawal, in addition to the loss of memory equivalent to 15
additional years of aging.25 Another study measured slow brain potentials in response to Go and
No Go conditions before, during and after marijuana smoking. The study found normal
responses both before and during smoking, but severely disrupted responses 20-40 minutes
later,26 during the period of peak intoxication, resembling those found in patients with lateral
prefrontal cortex lesions. Another study utilized BOLD fMRI to examine the brain activation
patterns in chronic marijuana users and matched control subjects during a set of visual attention
tasks.27 Although all subjects demonstrated similar task and cognitive test performance, active
and abstinent marijuana users showed decreased activation in the right prefrontal, medial and
dorsal parietal, and medial cerebellar regions (regions affected by THC), but greater activation in
various frontal, parietal and occipital brain regions. Investigators hypothesized that marijuana
users had lost some functionality in parts of the brain affected by marijuana use, which was
compensated in other regions of the brain. The long-term consequences of such damage was
not assessed, since the average age of marijuana users was less than 30. Another study
examined the ability of 25-day abstinent marijuana users to perform decision-making tasks,
simultaneously measuring brain activity using PET H215O.28 The marijuana group showed
greater activation in the left cerebellum and less activation in the right lateral orbitofrontal
cortex (OFC) and the right dorsolateral prefrontal cortex (DLPFC) compared with the control
group. The investigator concluded that heavy marijuana users had persistent decision-making
deficits and alterations in brain activity.28

Short term memory

Marijuana usage severely impacts short term memory,29 probably by interfering with the
hippocampus.30 Impairment is especially noted in tests that depend heavily on attention.31
Specifically, marijuana intoxication causes deficits in spatial learning tasks,32 delays in matching
or non-matching tests,32-33 and impaired performance in a radial arm maze in rodents.34

Long term cognitive function

Studies have found that regular cannabis use can cause small but significant impairments in
cognitive function that may persist after drug use stops.35 Heavy cannabis use in adolescence
may induce subtle changes in the adult brain circuits resulting in altered emotional and cognitive
performance and enhanced susceptibility for more harmful drugs of abuse in certain
individuals.36 Several studies have found deficits in attention and memory in heavy marijuana
users.37-39 However, normalization of cognitive function has been found with prolonged
abstinence (after 28 days),38-40 although other studies have observed persistent cognitive
deficits.41 Another study found that chronic cannabis use had little effect on cognitive function
except for possible decrements in the ability to learn and remember new information.42 A 38-
year study of more than 1,000 New Zealanders found that adolescents who used marijuana at
least four days per week lost an average of eight IQ points between the ages of 13 and 38.43
Those people who began heavy smoking of marijuana only in adulthood did not suffer a loss of
IQ. Loss of IQ was not reversible once marijuana use was ceased.43
Psychiatric illness

Some marijuana users can suffer from cannabis psychosis when they take large doses over a
period of time, with symptoms characteristic of paranoid schizophrenia.44 A recent study found
that marijuana use significantly increased the risk of developing mental health problems among
those young people who possessed a genetic high risk for schizophrenia (familial risk factors).45
Among cannabis users who developed cannabis-induced psychosis, 44.5% developed
schizophrenia-spectrum disorders, with about half of those being diagnosed more than a year
after seeking treatment for their cannabis-induced psychosis.46 A study using a sample of 880
adolescents in Melbourne, Australia found that lifetime cannabis use and the frequency of
cannabis use in the last year were associated with psychotic-like experiences (primarily the
experience of auditory and visual hallucinations).47 Another study examined the association
between cannabis use and psychosis in 3,800 participants involving a subset analysis of 228
sibling pairs over a 21-year period of time. The results showed that early use of marijuana was
associated with psychosis-related outcomes in young adults.48

Another study examined the associations between cannabis use and the development of mood
and anxiety disorders.49 The study found no association between cannabis used and the
development of anxiety disorders, although there was a significant correlation with the
development of depression and bipolar disorder.49 Another study found an association between
cannabis use and the development of panic attacks.50

Marijuana abuse and withdrawal

Although originally believed not be addictive, marijuana studies have shown that a substantial
percentage of users suffer from abuse or dependence.51 An Australian studied found that 10.7%
of marijuana users users suffered from substance abuse and another 21% suffered from
substance dependence.52 Another study, in the USA, found that 46% of those interviewed had
ever used marijuana and 9% of those users became dependent.53 In addition, studies have
shown that addicted individuals suffer a clinically significant withdrawal syndrome, which
includes craving for cannabis, decreased appetite, sleep difficulty and weight loss, and
sometimes anger, aggression, increased irritability, restlessness and strange dreams.54 A study
of teens showed that the overall severity of withdrawal was correlated with irritability,
depression, twitches and shakes, perspiring, and thoughts and cravings for cannabis.55 Animal
studies have shown that THC withdrawal leads to physiological symptoms similar to those seen
in animals suffering from opiate withdrawal.56 The symptoms of withdrawal can be lessened by
using the CB1 receptor agonist THC, demonstrating that cannabis use results in true addictive
withdrawal.57 A recent study has shown that the withdrawal symptoms are comparable to those
seen in tobacco withdrawal.58
Gateway hypothesis:

There is a tendency for marijuana users to go on to use other addictive drugs, following their
initial experience with marijuana.59 Whether marijuana use predisposes individuals to drug
abuse as a "gateway drug" or whether it is just the most easily available illicit drug, is not
completely known. However, a study of 311 pairs of same-sex twins found that the twins with
earlier marijuana use (before age 17 years) were 2–5 times more likely to use other illicit drugs,
especially psychostimulants.60

Concomitant drug use

A large percentage of Ecstasy/MDMA users (90-98%) also use marijuana.61 Studies have found
that each drug is functionally damaging, and polydrug users generally display cumulative
neurobiological impairments.61 Another study found that those who use both drugs suffer from
immunological impairments characterized by a significant decrease in interleukin-2 and an
increase in anti-inflammatory transforming growth factor-β1, along with a decrease in the
number of total lymphocytes, CD4+ and natural killer cells.62 Probably as a result of these
immunological impairments Ecstasy/cannabis users suffered a significantly higher rate of mild
infections.

Driving & cannabis

In Europe, three million people use cannabis every day and more than two thirds of those drive
after having smoked cannabis.63 Over 50% of drivers in Austria, Belgium, Germany, Switzerland
and the United Kingdom suspected of driving under the influence of drugs have been found to
have THC in their bloodstream.63 Numerous studies have shown that driving under the
influence of marijuana use results in a significant increase in motor vehicle accidents especially
those resulting in fatalities or serious injuries, even with low blood concentrations of THC.63-66
These studies have been done around the world, including Canada,64 Norway,65 and France.66

Use during pregnancy

A study conducted in the Netherlands found that 2.9% of women used cannabis both before and
during pregnancy.67 Factors coincident with cannabis use included use by the biological father,
being single, childhood trauma, delinquency, and lower educational level.67 The reason why
cannabis use is of concern is because it has been shown that THC crosses the placenta, thus
entering the fetus during development.68 It has also been found that THC is secreted in breast
milk, so it would fed to the newborn during breast feeding.68

A study at the University of Pittsburg examined the effect of prenatal marijuana exposure on
subsequent child intelligence.69 Heavy marijuana use (one or more cigarettes per day) during
the first trimester was associated with lower verbal reasoning scores on the Stanford-Binet
Intelligence Scale at age 6. Heavy use during the second trimester predicted deficits in the
composite, short-term memory, and quantitative scores. Third-trimester heavy use was
negatively associated with the quantitative score, indicating that prenatal marijuana exposure
has a significant effect on subsequent school-age intellectual development.69 Another study
found that prenatal marijuana exposure in the first and third trimesters predicted significantly
increased levels of depressive symptoms in 10-year olds.70 A 2006 survey of the literature
revealed that cannabis use during pregnancy was associated with a number of negative
outcomes in the child, including symptoms of inattention, impulsivity, deficits in learning and
memory, and a deficiency in aspects of executive functions.71 Another study found no effect of
marijuana on IQ, but did find that prenatal use negatively impacted executive functions,
influencing the application of these skills in problem-solving situations requiring visual
integration, analysis, and sustained attention.72

Use during adolescence

Adolescent exposure to cannabinoid compounds has been shown to affect the postnatal
development of opioid neurons.73 These alterations are likely to produce important long-lasting
functional changes in these neurons in the adult brain,74 including alterations in neuroendocrine
control,75 pain sensitivity,76 and reward processes.73, 77 Animal studies have shown that
cannabis exposure during adolescence can produce lasting memory deficits and hippocampal
alterations78 that affect memory and social interaction.79

Hormonal effects

Since THC affects the hypothalamus, which directly or indirectly modulates anterior pituitary
function, it has been hypothesized that it might affect human endocrine function. Animal and
human studies have shown that THC suppresses the reproductive hormones, prolactin, growth
hormone, and the thyroid axis, while the hypothalamic pituitary-adrenal axis is activated.80
However, it appears that in humans many of these effects are transitory, likely due to the
development of tolerance with continued use of the drug.80

Cancer risks
Although smoking marijuana doesn't have the same degree of risk as smoking tobacco (because
of the frequency of usage), smoking anything over long periods of time does add to risks of
contracting forms of cancer of the respiratory tract. Studies have suggested that smoking
marijuana increases the risk of both oral cancers81 and lung cancer.82 This is because marijuana
smoke contains carcinogenic materials, including vinyl chlorides, phenols, nitrosamines, reactive
oxygen species, and various polycyclic aromatic hydrocarbons, including Benzo[a]pyrene, which
is present in marijuana tar at a higher concentration than in tobacco tar.83 Ammonia was found
in marijuana smoke at levels up to 20-fold greater than that found in tobacco.84 Hydrogen
cyanide, NO, NO x , and some aromatic amines were found in marijuana smoke at
concentrations 3-5 times those found in tobacco smoke.84 However, absolute correlation of
marijuana smoking with cancer risks are complicated by concomitant tobacco smoking and
increased alcohol use among marijuana users.83

Adverse cardiovascular events

Some studies have suggested that marijuana might be a trigger for adverse cardiovascular
events, including tachyarrhythmias, acute coronary syndrome, and vascular complications,
especially in older users, and may be a risk factor in congenital heart defects for their children.85
Mixing marijuana with cocaine can cause cardiac problems, including the death of an otherwise
healthy 31 year old male86 and an acute myocardial infarction in a 21-year old male.87

Stroke

Ischemic stroke is found almost exclusively in people of advanced age. However a number of
reports have shown an association between cannabis abuse and ischemic stroke in young
people88 (one at the age of 1589). Using Doppler sonography scientists were able to determine
that cerebrovascular resistance and systolic velocity were significantly increased in marijuana
abusers compared to the control subjects and that cerebral perfusion observed in 18-30 year old
marijuana abusers was comparable to that of normal 60 year-olds.90 Another study showed that
6 of 10 subjects experienced reduced cerebral blood velocity and dizziness following marijuana
use.91 One heavy cannabis user was found to have a right temporal lobe hemorrhage, which
was cleared within three months by reducing cannabis use from 2–6 cannabis cigarettes per day
to 3–4 cigarettes per week.92

Oral health

Marijuana users generally have poorer oral health than non-users, with an increased risk of
dental caries (cavities) and periodontal diseases, along with dysplastic changes and pre-
malignant lesions within the oral mucosa.93 In addition, users are prone to oral infections,
possibly due to immunosuppressive effects.93

Medical Marijuana Survey 1998-2008

Marijuana studies 1998-2008Marijuana studies 1998-2008

In any review of the literature, it is possible that reviewer bias can enter the picture and distort
the overall impact and conclusions of the review. To mitigate potential reviewer bias, the author
initiated a complete Ovid-Medline search of marijuana/cannabis research in February 2009 for
the years 1998-2008. Studies were categorized as being "Very Negative," "Mostly Negative,"
"Neutral," "Mostly Positive," or "Very Positive." Data was collated and is presented in the figure
to the right. The data shows that research on the medical effects of marijuana is becoming
increasingly negative and decreasingly positive over the last 11 years of medical research. In
addition, the number of studies examining the medical aspects of marijuana has increased
markedly over the last 5 years, dramatically expanding our knowledge of the mostly negative
aspects of marijuana usage (see original data).94 The United States Department of Justice has
examined studies on medical marijuana us and abuse and has concluded, "At present, there are
no FDA-approved marijuana products, nor is marijuana NDA evaluation at the FDA for any
indication. Marijuana does not have currently accepted medical use in in the United States or a
currently medical use with severe restrictions."95 You can read their assessment here.

Legalize marijuana?

The California state legislature, in its infinite wisdom, is considering a bill (AB 390)96 to legalize
the growing of cannabis, its use, and sale. In return, the state expects to get over a billion dollars
from the sale of permits and taxes. Besides the revenue, they expect to save millions of dollars
from not having to enforce marijuana laws. And, of course, we know that all the people who
grow marijuana will do so legally by paying the several thousand dollar permit fee! Although the
sale of marijuana is restricted to those 21 years old and older, the penalties for selling to
underage persons is $100 or less. As a result of such lenient penalties, it is clear that adolescents
will be able to obtain marijuana more easily, leading to increased use, which is especially
troublesome given its effect upon the maturing brain. What the legislature seems to have
ignored in its financial analysis is the almost astronomical costs that will be incurred through
increased health care and mental health costs that will result from increased marijuana use in
the population of California. In addition, the number of people driving under the influence of
marijuana will increase dramatically, as it has in Europe, since its legalization there. The cost in
terms of increased deaths from automobile accidents could be in the hundreds to thousands of
lives lost. What are they thinking?
Conclusion Top of page

Having received dozens of emails saying how good marijuana is (mostly from "Christians"), I have
felt the need for a thorough review of the scientific literature regarding the positive and negative
aspects of marijuana use. The vast majority of studies show that there is no such thing as
"medical marijuana." In general, physicians in the United States are not thrilled with the idea
that marijuana should be allowed to be prescribed, since only 36% take that stance.97 The act of
smoking marijuana is fraught with so many adverse side effects that it really isn't useful in
treating symptoms in any specific disease for the vast majority of sufferers. However, the active
ingredient in marijuana (THC) has been shown to be useful for some patients who suffer from
chronic pain, especially in refractory cases of multiple sclerosis, and in patients who are suffering
from AIDS-related wasting syndrome. Even in those diseases, a minority of patients actually
derive a benefit that is without unwanted side effects. THC's use as an anti-emetic for patients
suffering nausea from cancer chemotherapy or as a way to lower intraocular pressure for
glaucoma has been replaced by far superior new medicines that don't have the negative side
effects.

Marijuana - What's a Parent to Believe?As a recreational drug, marijuana is not quite as benign
as most of its proponents would claim. Heavy marijuana use results in long-term effects on the
brain, including lower responses in those areas which are affected by THC. Although users are
able to compensate somewhat through the use of other brain areas, the long term effects of this
damage, as users age, has not been determined. This damage may be responsible for
impairments noted in short-term and long-term memory, along with a host of possible other
psychiatric illnesses. A proportion of marijuana users become addicted and suffer from classic
withdrawal symptoms upon abstinence. For a minority of users, marijuana is a gateway drug,
and they proceed to use and abuse more powerful psychostimulants. Besides its effects upon
the brain, marijuana use can lead to increased risks for respiratory cancers and may have some
adverse cardiovascular and cerebrovascular effects in some users. Marijuana use during
pregnancy has been shown to result in lower child intelligence, while increasing the incidence of
mental health problems. According to the DOJ, "In sum, at present, marijuana lacks an
acceptable level of safety even under medical supervision."95 The idea that marijuana is a
harmless recreational pastime has been disproved through continuing scientific research.

Related Pages Top of page

Is It Okay for Christians to Use Marijuana and Other Drugs?

Cannabis: an apology, The Independent, Sunday, 18 March 2007.

Denial of Petition To Initiate Proceedings To Reschedule Marijuana, U.S. Department of Justice,

July 8, 2011.

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See original data and additional figures in MarijuanaSurvey2009.xls (Microsoft Excel File 138 kb).

Michele M. Leonhart. Denial of Petition To Initiate Proceedings To Reschedule Marijuana, U.S.

Department of Justice, July 8, 2011.

AB 390 text.

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http://www.godandscience.org/doctrine/medical_marijuana_review.html

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