The active ingredient in marijuana cuts tumor growth in common lung
cancer in half and significantly reduces the ability of the cancer to
spread, say researchers at Harvard University who tested the chemical in
both lab and mouse studies.
They say this is the first set of experiments to show that the
compound, Delta-tetrahydrocannabinol (THC), inhibits EGF-induced growth
and migration in epidermal growth factor receptor (EGFR) expressing
non-small cell lung cancer cell lines. Lung cancers that over-express
EGFR are usually highly aggressive and resistant to chemotherapy.
THC that targets cannabinoid receptors CB1 and CB2 is similar in
function to endocannabinoids, which are cannabinoids that are naturally
produced in the body and activate these receptors. The researchers
suggest that THC or other designer agents that activate these receptors
might be used in a targeted fashion to treat lung cancer.
"The beauty of this study is that we are showing that a substance of
abuse, if used prudently, may offer a new road to therapy against lung
cancer," said Anju Preet, Ph.D., a researcher in the Division of
Experimental Medicine.
Acting through cannabinoid receptors CB1 and CB2, endocannabinoids
(as well as THC) are thought to play a role in variety of biological
functions, including pain and anxiety control, and inflammation.
Although a medical derivative of THC, known as Marinol, has been
approved for use as an appetite stimulant for cancer patients, and a
small number of U.S. states allow use of medical marijuana to treat the
same side effect, few studies have shown that THC might have anti-tumor
activity, Preet says. The only clinical trial testing THC as a treatment
against cancer growth was a recently completed British pilot study in
human glioblastoma.
In the present study, the researchers first demonstrated that two
different lung cancer cell lines as well as patient lung tumor samples
express CB1 and CB2, and that non-toxic doses of THC inhibited growth
and spread in the cell lines. "When the cells are pretreated with THC,
they have less EGFR stimulated invasion as measured by various in-vitro
assays," Preet said.
Then, for three weeks, researchers injected standard doses of THC
into mice that had been implanted with human lung cancer cells, and
found that tumors were reduced in size and weight by about 50 percent in
treated animals compared to a control group. There was also about a 60
percent reduction in cancer lesions on the lungs in these mice as well
as a significant reduction in protein markers associated with cancer
progression, Preet says.
Although the researchers do not know why THC inhibits tumor growth,
they say the substance could be activating molecules that arrest the
cell cycle. They speculate that THC may also interfere with angiogenesis
and vascularization, which promotes cancer growth.
Preet says much work is needed to clarify the pathway by which THC
functions, and cautions that some animal studies have shown that THC can
stimulate some cancers. "THC offers some promise, but we have a long
way to go before we know what its potential is," she said.
A recent study which was published in the “Annals of Oncology”
finds that the primary active ingredient in marijuana –
tetracannabinol, or THC – may help cancer patients improve their
appetites and sleep habits.
Some of the many unpleasant
side-effects of undergoing chemotherapy are appetite suppression, the
inability to enjoy food, and sleeplessness. Dr. Wendy Wismer, who is a
professor at the University of Alberta at Edmonton, lead a team which conducted a study where 21 patients were randomly administered either a THC pill or a placebo.
This was done two times a day for two and a half weeks.
While the overall caloric intake
between subjects in the control and experimental groups did not
significantly vary, many who were given the THC pill reported that they
found the food that they did eat tasted better. They also reported
improved patterns of sleep and relaxation.
These findings are not considered to be
revolutionary, but they may serve to further the cause of individuals
and organizations which advocate the use of medicinal marijuana.
It is also promising for people who
are currently undergoing chemotherapy or will in the future, as the
study suggests that monitored THC consumption can alleviate some of the
discomfort often associated with the treatment.
The largest study of its kind has
unexpectedly concluded that smoking marijuana, even regularly and
heavily, does not lead to lung cancer.
The new findings “were against our expectations,” said Donald Tashkin of the University of California at Los Angeles, a pulmonologist who has studied marijuana for 30 years.
“We hypothesized that there would be a
positive association between marijuana use and lung cancer, and that
the association would be more positive with heavier use,” he said.
“What we found instead was no association at all, and even a suggestion
of some protective effect.”
Federal
health and drug enforcement officials have widely used Tashkin’s
previous work on marijuana to make the case that the drug is dangerous.
Tashkin said that while he still believes marijuana is potentially
harmful, its cancer-causing effects appear to be of less concern than
previously thought. Earlier work established that marijuana
does contain cancer-causing chemicals as potentially harmful as those
in tobacco, he said. However, marijuana also contains the chemical THC,
which he said may kill aging cells and keep them from becoming
cancerous. Tashkin’s study, funded by the National Institutes of Health‘s National Institute on Drug Abuse,
involved 1,200 people in Los Angeles who had lung, neck or head cancer
and an additional 1,040 people without cancer matched by age, sex and
neighborhood. They were all asked about their lifetime
use of marijuana, tobacco and alcohol. The heaviest marijuana smokers
had lighted up more than 22,000 times, while moderately heavy usage was
defined as smoking 11,000 to 22,000 marijuana cigarettes. Tashkin
found that even the very heavy marijuana smokers showed no increased
incidence of the three cancers studied. “This is the largest case-control study
ever done, and everyone had to fill out a very extensive questionnaire
about marijuana use,” he said. “Bias can creep into any research, but
we controlled for as many confounding factors as we could, and so I
believe these results have real meaning.” Tashkin’s group at the David Geffen School of Medicine at UCLA
had hypothesized that marijuana would raise the risk of cancer on the
basis of earlier small human studies, lab studies of animals, and the
fact that marijuana users inhale more deeply and generally hold smoke
in their lungs longer than tobacco smokers — exposing them to the
dangerous chemicals for a longer time. In addition, Tashkin said,
previous studies found that marijuana tar has 50 percent higher
concentrations of chemicals linked to cancer than tobacco cigarette tar. While no association between marijuana smoking and cancer was found, the study findings, presented to the American Thoracic Society
International Conference this week, did find a 20-fold increase in lung
cancer among people who smoked two or more packs of cigarettes a day. The study was limited to people younger
than 60 because those older than that were generally not exposed to
marijuana in their youth, when it is most often tried.
Ever since the mid 70s, medical scientists have been well aware of the
beneficial effects of cannabinoid compounds over cancerous cells. Thanks
to modern science, over a dozen studies conducted during recent years
have been able to partially reveal just how it works. Yet cannabis is
still not endorsed by pharmaceutical companies as a cancer cure, and
since it is not promoted through mainstream channels, very few people
are aware of its benefits. Consequently, it is not sought after as an
alternative to disfiguring chemotherapy and other harmful drugs.
Laboratory
tests conducted in 2008 by a team of scientists formed as a joint
research effort between Spain, France and Italy, and published in The Journal Of Clinical Investigation,
showed that the active ingredient in marijuana, known as
tetrahydrocannabinol or THC, can function as a cure for brain cancer by
inducing human glioma cell death through stimulation of autophagy.
The
study concluded that via the same biochemical process THC could
terminate multiple types of cancers, affecting various cells in the
body. Other studies have shown that cannabinoids may work by various
mechanisms, including inhibiting cell growth, inducing cell death, and
inhibiting tumor metastasis.
What is amazing is that while
cannabinoids effectively target and kill cancerous cells, they do not
affect healthy, normal cells and may actually protect them against
cellular death. Moreover, cannabinoids are also researched for their
pain-modulation and anti-inflammatory abilities as they bind to special
receptors in the brain, much like opioid derivatives that are commonly
prescribed today.
Further evidence to support the effects of
cannabis extract on malignant cells comes from the real life experience
of individuals who have successfully overcome cancer by using cannabis oil.
Examples include a patient, who managed to completely cure his skin
cancer by simply applying cannabis oil onto the affected areas of the
skin, as well as another, who recovered from a severe head injury with
the aid of hemp oil.
One
of the cannabinoids that has displayed amazing medical properties is
cannabidiol, or CBD - a non-psychoactive compound that is regarded by
some as the medical discovery of the 21st century, and with good reason.
Research indicates that CBD can relieve convulsions, reduce
inflammation, lower anxiety and suppress nausea, while also inhibiting cancer
development. In addition, CBD has exhibited neuroprotective properties,
relieving symptoms of dystonia and proving just as effective as regular
antipsychotics in the treatment of schizophrenia.
What stands
out is that from the vast amount of research and data available, as well
as the personal experiences of cancer survivors, is that no
chemotherapy currently being used medically can match the non-toxic
anti-carcinogenic and anti-tumorigenic effects of these natural plant compounds.
Cannabis could be used to treat many forms of cancer, new research suggests.
The drug contains an ingredient which slows tumour growth and prevents the reproduction of cancer cells, doctors say.
Its effects are seen in all cancers but particularly in those of the lung and brain, and leukaemia, it is claimed.
But scientists warned against smoking the drug, saying the only safe version was that created in the lab.
Researcher Dr Wai Man Liu said: 'I'm in no way encouraging
people to take up smoking the ganja – there would be more harm than
good.'
Previous research has shown cannabis-based medicines can
help cancer patients as a painkiller, appetite stimulant and in reducing
nausea.
The drug has also long been used by multiple sclerosis and arthritis sufferers to reduce pain.
Its medicinal benefits come from the main active ingredient,
THC. The latest research, by St George's University of London, shows
that THC can weaken cancer cells to make traditional chemotherapy more
effective.
Dr Liu said: 'It's another weapon against the armour of
cancer. We are quite close but need to jump through certain hoops. I
believe it could be used in two to three years.'
Dr Joanna Owens, from Cancer Research UK, said the latest
studies were encouraging but needed to be followed up with more trials.
She added: 'Making cancer cells more vulnerable to chemotherapy or
radiotherapy is a great concept but it is still early days.'
Scientists working in the UK have revealed that cannabis has the potential to destroy leukemia cells.
The team – based at Queen Mary’s School of Medicine and Dentistry in
London – have followed up on their previous findings that the main
active ingredient in cannabis, tetrahydrocannabinol (THC) has the potential to be used effectively against some forms of cancer.
Use of cannabis as
a therapeutic agent continues to be controversial due to its
psychoactive side effects and consequent legal status, however, leader
of the team, Dr Wai Man Liu, explains: “It is important to stress that
these cannabis-like substances are far removed from the cannabis that is
smoked. These novel compounds have been specifically designed to be
free of the psychoactive features, whilst maintaining anti-cancer
action.”
THC has previously been shown to attack cancer cells by interfering
with important growth-processing pathways, however its mechanism of
doing so has remained a mystery. Now, Dr Liu and his colleagues, using
microarray technology – allowing them to simultaneously detect changes
in more than 18,000 genes in cells treated with THC – have begun to
uncover the existence of processes through which THC can kill cancer
cells and potentially promote survival.
The researchers hope that the findings will provide a crucial step
towards the development of new therapies for many types of cancer. Dr
Liu said: “Ultimately, understanding the fundamental mechanisms of these
compounds will provide us with insights into developing new drugs that
can be used to effectively treat cancers.”
Indica, Sativa and THC are words that
you will find everywhere in a cannabis seeds shop. But what ido these
words mean? We have created this page with the purpose of informing you
about cannabis, so you can select the strain that is 100% satisfying for
you. Let's start with order. Indica and Sativa are the names that are
mostly related to this plant. Nowadays many of the scientists agree that
there is only one kind of cannabis, the Cannabis Sativa L. However, in
an important part of the literature and in the common use you can find
the classification of cannabis in 3 species: Indica, Sativa and
Ruderalis.
INDICA
An indica plant is usually not too
tall (about 1,5 mt max) with the typical shape of a Christmas tree.
These plants are originated on high hills or mountain areas (ex. Nepal,
North India etc).They are robust and easy to grow. They develop big
buds that are really dense, with the calyxes pressed together. They
tolerate a low level of stress pretty will. The effect of an indica
plant is so called "stoned" or "corporal", with a strong body and mind
relaxation. If we compare it with a wine, and Indica is a heavy red
selection.
SATIVA
A sativa plant is usually tall (1,5 mt
or taller) with short branches. These plants originate in tropical
areas (ex. Caribbean, Thailand islands, etc). There are more buds sites
than on an indica, but the buds tend to be less dense. The effect of a
sativa plant is a so called "cerebral" or "high", that is milder than an
indica on the body but with a more pronounced effect on the brain. It
goes from a creative feeling to a trippy feeling according to the
strength. If we compare it with a wine, a sativa is the champagne of
cannabis.
RUDERALIS
Cannabis Ruderalis is not typically
meant for marijuana production. The Ruderalis is a specie of cannabis
originally from Russia, with a height around a half meter, no side
branches and little or no buds. It is used in the production of hybrids
to make them more resistant, or to let them flower according to their
age (rather than the number of hours of dark that they receive, like
every other cannabis plant).
THC and other cannabinoids
THC
is the acronym of delta-9-tetrahydrocannabinol, and is is the main
psychoactive substance found in the cannabis plant. For the plant
itself, the THC is a natural method of protecting itself from pathogenic
agents or herbivores animals. It also offers a really good protection
against the sun's UVB rays. Men have grown cannabis for thousands of
years to extract the THC out of it. As you may have noticed, we show
the THC level for most of the strains in our catalog. We need to specify
something about this information. Every strain, every single seed have a
potential. It's up to the grower then, if the potential will be fully
released or not. If you read that a strain have 10% of THC, rating it
doesn't mean that every plant of that strain will have 10% of THC. It
mean instead that that strain have a potential of producing about 10% in
THC. In the hands of an expert, in the right conditions, these seeds
will produce 10% or even more. In a less favorable environment, the same
seeds will produce for example 8%. All these words are a reminder that a
seed is not a computer, where the values are only 0 and 1. It's a live
creature and the final result will be the combination of thousands of
little variables. We proudly say that we can offer you the best
potential there is, but we can never guarantee (and nobody can) that you
will always achieve the values in the description.
Further, you should consider that THC
is the main psychoactive substance found in the cannabis plant but not
the only one. A cannabis bud contains more than 400 different substances
which 61 of them are cannabinoids. The effect of the marijuana is
determined by the combination and interactions of all these elements.
Beside the THC, a major role is played by cannabidiol (CBD), and
cannabinol (CBN). These substances have deep relaxation effects
themselves, and they are heavily involved in the THC absorption. So the
final effect is given by a subtle combination of different cannabinoids.
We won't go in this topic further
because we don't want anyone to get bored, but always remember the
conclusion: we can never say that a strain is more "strong" than another
just because it has a higher level of THC.
Lisa M. Eubanks, Ph.D., et al. stated in an Aug. 9, 2006 Molecular
Pharmaceutics journal article titled "A Molecular Link Between the
Active Component of Marijuana and Alzheimer's Disease Pathology" (PDF
143KB):
"In contrast to previous studies aimed at utilizing cannabinoids in
Alzheimer's disease therapy, our results provide a mechanism whereby the
THC molecule can directly impact Alzheimer's disease pathology.[...]
It is noteworthy that THC is a considerably more effective inhibitor
[...] than the approved drugs for Alzheimer's disease treatment,
donepezil and tacrine, which reduced [protein deposits in the brain] by
only 22% and 7%, respectively, at twice the concentration used in our
studies. [...]
THC and its analogues may provide an improved therapeutic for
Alzheimer's disease [by] simultaneously treating both the symptoms and
progression of Alzheimer's disease." b
Aug. 9, 2006 Lisa M. Eubanks
Maria L. de Ceballos, Ph.D., et al. wrote in their Feb. 23, 2005 article
"Prevention of Alzheimer's disease Pathology by Cannabinoids:
Neuroprotection Mediated by Blockage of Microglial Activation,"
published in the Journal of Neuroscience (Vol. 25 No. 8, pp.1904-1913):
"Our results indicate that cannabinoid receptors are important in the
pathology of AD [Alzheimer's disease] and that cannabinoids succeed in
preventing the neurodegenerative process occurring in the disease."
Feb. 23, 2005 Maria L. de Ceballos
The Oregon Department of Health Services stated in a June 14, 2000 press release:
"After reviewing the recommendations of an expert panel, we have decided
to add Agitation of Alzheimer's disease to the list of medical
conditions for which a doctor may write a statement of support for the
medical use of marijuana."
Current and former marijuana use: preliminary findings of a longitudinal study of effects on IQ in young adults
Peter Fried, Barbara Watkinson, Deborah James and Robert Gray
From the Department of Psychology, Carleton University, Ottawa, Ont.
Background: Assessing marijuana's impact on intelligence quotient (IQ)
has been hampered by a lack of evaluation of subjects before they begin
to use this substance. Using data from a group of young people whom we
have been following since birth, we examined IQ scores before, during
and after cessation of regular marijuana use to determine any impact of
the drug on this measure of cognitive function.
Methods: We determined marijuana use for seventy 17- to 20-year-olds
through self-reporting and urinalysis. IQ difference scores were
calculated by subtracting each person's IQ score at 9–12 years (before
initiation of drug use) from his or her score at 17–20 years. We then
compared the difference in IQ scores of current heavy users (at least 5
joints per week), current light users (less than 5 joints per week),
former users (who had not smoked regularly for at least 3 months) and
non-users (who never smoked more than once per week and no smoking in
the past two weeks).
Results: Current marijuana use was significantly correlated (p <
0.05) in a dose- related fashion with a decline in IQ over the ages
studied. The comparison of the IQ difference scores showed an average
decrease of 4.1 points in current heavy users (p < 0.05) compared to
gains in IQ points for light current users (5.8), former users (3.5) and
non-users (2.6).
Interpretation: Current marijuana use had a negative effect on global IQ
score only in subjects who smoked 5 or more joints per week. A negative
effect was not observed among subjects who had previously been heavy
users but were no longer using the substance. We conclude that marijuana
does not have a long-term negative impact on global intelligence.
Whether the absence of a residual marijuana effect would also be evident
in more specific cognitive domains such as memory and attention remains
to be ascertained.
Marijuana produces well-documented, acute cognitive changes that last
for several hours after the drug has been ingested.1,2,3 Whether it
produces cognitive dysfunction beyond this period of acute intoxication
is much more difficult to establish. Approaches to investigating
long-lasting effects include clinical assessment of long-term
users,4,5,6 observations of subcultures in countries where long-term
daily use of cannabis has been the cultural norm for decades7,8,9 and
marijuana administration studies in which subjects with a history of use
ranging from infrequent to extensive are given the drug in controlled
laboratory settings after various periods of abstinence.10,11,12 As
discussed in several reviews of the literature,1,13,14 the findings have
been equivocal.
Most studies that examined heavy marijuana users for possible cognitive
dysfunction lasting beyond the acute intoxication period assessed
subjects after an abstinence period of only a day or two.10,12,15,16 The
fact that cannabinoid metabolites have been detected in the urine of
long-term marijuana users after weeks or even months of
abstinence17,18,19 compromises the interpretation of these studies. To
account for potential pre-existing differences between users and
non-users, studies have typically matched the comparison group with the
user group in terms of non-marijuana variables.6,20 Suggestions for
improving study designs13,14 have emphasized both the need for
comparison groups to be as similar as possible to the drug-using group
and the need for a prolonged abstinence period. The most desirable
procedure would involve a longitudinal, prospective design in which
cognitive measures were available for all non-using and using subjects
before and after marijuana consumption had been initiated by the
users.15
The Ottawa Prenatal Prospective Study (OPPS), underway since 1978,
satisfies these criteria. This study permits both within-subject and
between-subject comparisons among relatively low-risk non-users and
users before, during and after quitting regular marijuana use. The
primary objective of the OPPS is the neuropsychologic assessment of
children exposed prenatally to marijuana or cigarettes. Women who used
and did not use marijuana and cigarettes volunteered to participate
during their pregnancy, and their children, now between the ages of 17
and 20 years, have been assessed since birth. Details of the recruitment
of the largely middle-class families, the assessment procedures and the
findings for the children from birth to adolescence have been
summarized elsewhere.21,22
The objectives of the current study were as follows: to determine if
current, regular marijuana use is predictive of decline in IQ from
pre-usage levels, to determine if a differential effect on IQ occurs
with heavy versus light current, regular marijuana use, and to determine
if any IQ effects persist after subjects cease using marijuana for at
least 3 months.
A potential pool of 74 young adults with urinalysis results,
self-reports of marijuana use and a broad measure of IQ obtained at both
a preteen (9–12 years) and a young adult (17–20 years) assessment was
available. Two subjects with inconsistencies between the self- report of
marijuana use and the urine screening results were excluded, as were
one subject who tested positive for cocaine and another who was taking
methylphenidate. Consequently, the final sample comprised 70 subjects
whose self-report of marijuana use and absence of hard drug use had been
validated by urinalysis results.
During the preteen period and before initiation of marijuana use, IQ was
measured by means of the Wechsler Intelligence Scale for Children-III
(WISC).23 When the subjects were young adults, IQ was evaluated with the
Wechsler Adult Intelligence Scale-III (WAIS).24 The outcome variable
for the examination of potential marijuana effects was an IQ difference
score, derived by subtracting the preteen WISC IQ score from the young
adult WAIS IQ score. Thus a positive difference score reflects an
increase in IQ over the approximately 10-year period, whereas a negative
score reflects a decrease.
Marijuana use was determined by 2 procedures that were part of an
extensive neuropsychologic battery given to the 17– to 20-year-olds. The
first consisted of a questionnaire completed by the subject, which
asked for details of current and past marijuana use, as well as other
drug use. The second was a urine sample analyzed for the presence of
cannabinoids, amphetamines, opiates, cocaine and cotinine (a metabolite
of nicotine). All metabolite concentrations were adjusted for creatinine
to control for urine dilution. Although these procedures did not assess
the strength of the marijuana used by the OPPS subjects, an estimate
was suggested by Health Canada's analysis of marijuana seized by police
between 1996 and 1999, which revealed an average of 5% to 6%
tetrahydrocannabinol (THC).
Marijuana measures treated as continuous variables were self-report of
mean number of joints currently smoked per week, self-report of length
of time (months) that marijuana had been smoked and total estimated
number of joints smoked (mean number of joints smoked per week
multiplied by number of weeks of use). The mean number of joints
currently smoked per week was also treated as a categorical variable, as
follows: the subjects were grouped as light current regular users,
heavy current regular users, former regular users or non-users.
Categorization of the current marijuana users as light or heavy users
was based on both the self-report and the urinalysis data. The
urinalysis data were bimodally distributed: 11 subjects had cannabinoid
to creatinine ratios between 4 and 54 ng/mg, and 13 subjects had ratios
between 147 and 705 ng/mg. These 2 groups of subjects were used to
validate the categorization based on self-reports. Defining heavy
regular use as at least 5 joints per week (n = 15) and light regular use
of any amount less than 5 joints at least once a week (n = 9) optimized
concordance with the bimodal urine division as indicated by 2 analysis.
Eight (73%) of the 11 subjects with the lower metabolite values smoked
fewer than 5 joints per week, and 12 (92%) of the 13 subjects with the
higher metabolite values smoked an average of 5 or more joints per week
(p = 0.001).
Of the 70 subjects, 37 were non-users who had never used marijuana
regularly (where regular use was defined as at least once a week) and
who had not used any marijuana in the past 2 weeks; 9 were former users
who had smoked marijuana regularly in the past but had not smoked for at
least 3 months before the young adult assessment; 9 were light current
users; and 15 were heavy current users.
The assessments were conducted in laboratories at Carleton University,
Ottawa. Given that the testing sessions commenced in the early morning
and that all subjects reported no use of marijuana on the day of
testing, it is unlikely that the subjects were assessed while in an
acute state of intoxication.
The validity of self-reporting for current marijuana use was examined
with 2 approaches. The initial selection of the 70 subjects involved a
criterion of concordance between self-reports of marijuana use and urine
screening results (see above). The second measure of concordance was a
high correlation between reported current marijuana use and the
cannabinoid to creatinine ratio found with urinalysis (r = 0.70, p <
0.001). Although self-reports of earlier use could not be directly
confirmed pharmacologically, their reliability is enhanced by the
validity of the self-reporting for current marijuana use.
In examining the relation between marijuana use and IQ difference
scores, we considered a variety of potentially confounding variables,
including variables related to socioeconomic status, such as family
income and parental education; the subject's education level (number of
years of education at the time of the young adult assessment); age and
sex of the subject; mother's age at the time of the subject's birth;
maternal use of cigarettes, marijuana and alcohol during pregnancy; and
the subject's use of tobacco and alcohol and exposure to secondhand
marijuana smoke. In the subsequent analyses, we controlled for any
potential confounding factor that was related to both the marijuana
independent variable (at ? = 0.1) and the IQ difference score (at ? =
0.05).25
Hierarchical regression (a statistical approach to measure the impact of
marijuana use after considering potential confounders) was used to
examine the predictive relation of quantity (both mean number of joints
per week and total joints over lifetime) and duration (period of use) of
current marijuana use to the IQ difference score. Differential effects
on the IQ difference score of light current use, heavy current use and
former use as contrasted to non-use were examined with Dunnett's 2-sided
multiple comparison procedure26 with analysis of variance (ANOVA) and
analysis of covariance (ANCOVA) when required to control for confounding
variables.
Analyses in which number of joints smoked per week was used both as a
continuous and as a categorical variable revealed significant
associations of this variable with the IQ difference score.
When number of joints smoked per week was treated as a continuous
variable, regression analyses revealed a significant negative
association with the IQ difference score (r = –0.24, p < 0.05) after
accounting for potentially confounding variables. In these analyses, no
predictive relation with the IQ difference score was found for the
self-reported period of marijuana use or the estimated total number of
joints smoked.
For analyses in which number of joints smoked per week was treated as a
categorical variable, ANOVA with Dunnett's procedure26 indicated that
the mean IQ difference score for the heavy current user group was
significantly different from that for non-users (–4.0 v. 2.6, p <
0.05), whereas no significant differences were evident in comparisons
with the light current users and former users (5.8 v. 2.6 and 3.5 v. 2.6
respectively) (Table 1). The characteristics of the 4 groups (light
current users, heavy current users, former users and non-users) are
presented in Table 1. Of particular importance to the present study is
the fact that preteen IQ, assessed before marijuana use, did not differ
across the groups. Although some characteristics did differ across the 4
groups (such as father's and mother's education), none of these was
associated with the IQ difference score; therefore, they were not used
as covariates.
Although there was no overall difference in IQ difference score between
former users and non-users, a subgroup of former users, those who had
used at least 5 joints per week (heavy use), was analyzed separately;
again, there was no significant difference relative to non-users
(t-test, p = 0.7). This lack of a negative impact among the former heavy
users is striking, as they had smoked, on average, an estimated 5793
joints over 3.2 years (mean of 37 joints per week); in contrast, the
current heavy users had smoked, on average, an estimated 2386 joints
over 3.1 years (mean of 14 joints per week).
In the present work, the use of commensurable IQ measures obtained
before and after initiation of marijuana use permitted examination of
the consequences of marijuana use in the context of pre-drug
performance. Of all the marijuana and non-marijuana variables
considered, only the quantity of current marijuana use, in terms of
number of joints smoked per week, was negatively related to change in IQ
from preteen to young adult. Not associated with change in IQ were
duration of marijuana use, the total quantity of marijuana used and
former use of marijuana. In addition, variables such as socioeconomic
status (family income and parental education), age of mother at time of
subject's birth, subject's prenatal exposure to drugs (nicotine,
marijuana and alcohol), preteen IQ score, age, sex, academic history,
other drug use and passive marijuana exposure were not predictive of
change in IQ score.
The IQ difference score for the heavy current users differed from that
for non-users, but no such differences were apparent between light
current users and non-users. The clinical significance for an individual
of such an effect on IQ scores is difficult to ascertain, but the
impact on society might be substantial. IQ scores are considered
normally distributed, with a mean of 100 and a standard deviation of 15,
and it is therefore estimated that 2.3% of individuals will score 70 or
below (2 standard deviations [SD]), and 6.7% will score 77.5 or below
(1.5 SD) on global intelligence tests. These are cutoff points at which
intervention and special education have typically been provided.27 Any
factors in a population that result in a 4-point decrease in IQ, as was
found with the heavy current marijuana users, would increase to 5.5% the
proportion of individuals with an IQ of 70 or below and to 11.0% those
with an IQ of 77.5 or below. A corresponding decrease in proportions
would be expected on the other end of the distribution (people with
higher IQ scores). For comparison, an IQ decrement of 5 points has been
observed in children exposed prenatally to 3 alcoholic drinks per day,28
of 3.75 points in offspring exposed prenatally to cocaine27 and of 2.6
points after low lead exposure.29
The IQ deficit among heavy current users in the present study likely
reflected residue of the drug in their bodies.10 Assuming use of at
least 5 joints per week by subjects in this group and given the
elimination half-life of THC in the plasma of long-term marijuana
users,30,31 such quantities and patterns of smoking are likely to result
in an accumulation of THC in the body.
Although the heavy current users experienced a decrease in IQ score,
their scores were still above average at the young adult assessment
(mean 105.1). If we had not assessed preteen IQ, these subjects would
have appeared to be functioning normally. Only with knowledge of the
change in IQ score does the negative impact of current heavy use become
apparent.
There were no differences in IQ score at the preteen assessment among
the future groups of users and the future non-users. This finding
suggests that, at least in a low-risk, white, predominantly middle-class
sample, IQ score before any marijuana use is not a predictor of future
marijuana use.
We investigated the possibility of a longer-lasting deficit, perhaps
representing a neurotoxic consequence on the central nervous system
(CNS), using data for the former users. The mean IQ difference score for
the former users did not differ significantly from that for the
non-users, which suggests a lack of long-term effects. Similarly, there
was no negative impact on IQ difference among former heavy users
relative to non-users (in contrast to the situation for current heavy
users). This lack of a long-lasting negative impact suggests the absence
of any CNS alteration as reflected by global IQ performance.
Both the negative effects of use of at least 5 joints weekly and the
lack of long-term effects found in this study should be interpreted
cautiously. The relatively small number of subjects for whom data were
available, the length of time that the drug was used, the estimated
total number of joints smoked and the young age of the subjects may
serve, individually or collectively, to moderate effects. Smoking at
least 5 joints weekly should not be interpreted as a definitive
threshold, as subjects were at low risk for other factors that could
have a negative synergistic effect on IQ score. It is also important to
emphasize that broad intellectual functioning may be less vulnerable to
the consequences of marijuana use than more specific cognitive domains,
such as attention and memory.7,13,14
The popularity of marijuana among youth has been increasing during the
past 4 years,32,33 and pressure on governmental agencies to assess the
medical uses of the drug and to reassess the legal status of the drug
has been growing.34 These trends emphasize the need to continue
investigating the cognitive consequences of both current and previous
marijuana use.
Medicine in the western world has forgotten almost all it once knew
about the therapeutic properties of cannabis. As a result of cannabis
prohibition we have lost not only a valuable agricultural crop but a
valuable medicine also. The history of cannabis in western medicine
lasted from the 1840s to the 1940s, during which period it was
extensively used to treat a wide variety of diseases.(1) According to
Prof. A.D.McDonald of Manchester University, writing as recently as
1941: "In the clinical experience of many alienists, a good preparation
of hemp is incomparably the best drug for depressive mental
conditions."(2) It was equally widely used in the treatment of physical
conditions.
NIDA Official Joint The western experience with cannabis as a
therapeutic substance must be seen against a background of traditional
use of the plant as a folk-medicine over many thousands of years.
Although the details are obscure it seems that such use was established
in China, India and the Middle East during the first millennium BC.(3)
It continues today throughout South Asia, Southern and Eastern Africa,
South America and the West Indies.(4) Cannabis is one of the mainstays
of the Unani Tibbi and Ayurvedic systems of medicine which in 1965 were
estimated to be the only form of medical care available to 80 per cent
of the population of India.(5) It was from India that cannabis as a
medicament was introduced to Europe and North America, although the
plant has been cultivated in these areas for fibre production for many
centuries. Surprisingly, it seems certain that neither its intoxicant
nor its medicinal properties were generally known in the West at the
beginning of the nineteenth century, although there are a number of
earlier references in herbals, particularly Culpeper's of 1652.(6)
The therapeutic use of cannabis was introduced into Western medicine in
1839 through a forty-page article by W B. O'Shaughnessy, a
thirty-year-old physician serving in Bengal.(7) His discussion of the
history of the use of cannabis products in the East reveals an awareness
that the drugs had not only been used in medicine for therapeutic
purposes, but had also been used for recreational and religious
purposes.
After studying the literature on cannabis and conferring with
contemporary Hindu and Muslim scholars, O'Shaughnessy tested the effects
of various hemp preparations on animals, before attempting to use them
to treat humans. Satisfied that the drug was reasonably safe, he
administered preparations of cannabis extract to patients, and
discovered that it had analgesic and sedative properties. O'Shaughnessy
successfully relieved the pain of rheumatism and stilled the convulsions
of an infant with this strange new drug. His most spectacular success
came, however, when he quelled the wrenching muscle spasms of tetanus
and rabies with the fragrant resin. Psychic effects resembling a curious
delirium, when an overdose was given, were treated with strong
purgatives, emetics with a blister to the nape of the neck, and leeches
on the temples.
O'Shaughnessy
W.B. O'Shaughnessy M.D. Professor of Chemistry and Natural Philosophy, Medical College, Calcutta.
"In 1839, W.B. O'Shaughnessy, MD., a thirty-year-old graduate of the
medical school in Edinburgh, under service to the British East India
Company, published his monograph 'On the Preparation of the Indian Hemp,
or Gunjah.'
This marked the introduction of hemp into conventional 19th Century
western medicine. O'Shaughnessy's monograph provided a summary of all
the knowledge available to him and reviewed his experiments with animals
before he performed human experiments with diseases, including
rheumatism, cholera, rabies and tetanus.
Some seven years before, at the end of his medical training in Scotland,
O'Shaughnessy invented intravenous fluid and electrolyte replacement
therapy during a cholera epidemic. In the years following his hemp
research, he went on to publish a pharmacopeia of Indian medicines. He
then changed careers, becoming an engineer, and brought the telegraph to
India, a service for which he was knighted. He then returned to
England, changed his name, and was married three times before dying at
the age of eighty-one." (The Marijuana Papers, ed. Mikuriya, 1973)
The use of cannabis derivatives for medicinal purposes spread rapidly
throughout Western medicine, as is shown in the report of the Committee
on Cannabis Indica of the Ohio State Medical Society, published in 1860.
In that report physicians told of success in treating stomach pain,
childbirth psychosis, chronic cough, and gonorrhea with hemp
products.(8) A Dr Fronmueller, of Fuerth, Ohio, summarized his
experiences with the drug as follows:
I have used hemp many hundred times to relieve local pains of an
inflammatory as well as neuralgic nature, and judging from these
experiments, I have to assign to the Indian hemp a place among the
so-called hypnotic medicines next to opium; its effects are less
intense, and the secretions are not so much suppressed by it. Digestion
is not disturbed; the appetite rather increased; sickness of the stomach
seldom induced; congestion never. Hemp may consequently be employed in
inflammatory conditions. It disturbs the expectoration far less than
opium; the nervous system is also not so much affected. The whole effect
of hemp being less violent, and producing a more natural sleep without
interfering with the actions of the internal organs, it is certainly
often preferable to opium, although it is not equal to that drug in
strength and reliability. An alternating course of opium and Indian hemp
seems particularly adapted to those cases where opium alone fails in
producing the desired effect.
It seems to have been assumed for some years that only Indian hemp (then
known as Cannabis indica) was of medicinal value. The fact that
American and European hemp (Cannabis sativa) were capable of producing
the same effects was not established until 1869, when Wood tried the
extract of 1.5 ounces of Kentucky-grown cannabis on himself and found
the effects unmistakable (they lasted for 24 hours). About one per cent
of this dose was found to be therapeutically effective in cases of
neuralgia.(9) In spite of this clear demonstration that American
cannabis could be as effective as the best Indian (also, incidentally,
that the male plant is as active as the female), the pharmacopoeia
specifications continued to require Indian hemp and the material used in
the preparation of extracts and tinctures used in American and European
medicine continued to be obtained from India.
Effective in Treating Many Illnesses
Cannabis was used during these years, with varying degrees of success in
the treatment of dysmenorrhoea,(10) strychnine poisoning(11),
menorrhagia(12), pericarditis following rheumatic fever(13), delirium
tremens(14), chloral and opium addiction(15), insomnia(16), dyspepsia,
indigestion and other stomach disorders(17), persecution mania(18),
phthisis(19), migraine and other headaches(20). The purpose for which it
chiefly established itself, however, was as a sedative and hypnotic, in
which role its superiority to the opiates was established to the
satisfaction of many physicians, notably Suckling(18) and Mattison(21).
According to Suckling:
With a wish for speedy effect, it is so easy to use that modern
mischief-maker, hypodermic morphia, that they (young physicians) are
prone to forget remote results of incautious opiate giving.
Would that the wisdom which has come to their professional fathers
through, it may be, a hapless experience, might serve them to steer
clear of narcotic shoals on which many a patient has gone awreck.
Indian hemp is not here lauded as a specific. It will, at times, fail.
So do other drugs. But the many cases in which it acts well, entitle it
to a large and lasting confidence. My experience warrants this
statement: cannabis indica is, often, a safe and successful anodyne and
hypnotic.(18)
The most influential of the nineteenth-century reports on the
therapeutic uses of cannabis was probably that of J. Russell Reynolds,
published in 1890. The author's position as Physician in Ordinary to HM
Queen Victoria and President of the Royal College of Physicians, in
addition to his thirty years of clinical experience with the drug, all
served to give credence to his emphatic statement that "Indian hemp,
when pure and administered carefully, is one of the most valuable
medicines we possess". Reynolds carefully listed both those conditions
in which he had found cannabis useful and those which he had not. He
recommended it in senile insomnia, neuralgia, migraine, gouty pains,
epileptoid and other spasms and convulsions (as distinct from true
epilepsy), spasmodic asthma and spasmodic dysmenorrhoea.
Advantages and Disadvantages
In their study of the medical applications of cannabis, physicians of
the nineteenth century repeatedly encountered a number of difficulties.
Recognizing the therapeutic potential of the drug, many experimenters
sought ways of overcoming these drawbacks to its use in medicine, in
particular the following:
* Cannabis products are insoluble in water.
* The onset of the effects of medicinal preparations of cannabis takes
an hour or so; its action is therefore slower than that of many other
drugs.
* Different batches of cannabis derivatives vary greatly in strength;
moreover, the common procedure for standardization of cannabis samples,
by administration to test animals, is subject to error owing to
variability of reactions among the animals.
* There is wide variation among humans in their individual responses to cannabis.
Despite these problems regarding the uncertainty of potency and dosage
and the difficulties in mode of administration, cannabis has several
important advantages over other substances used as analgesics,
sedatives, and hypnotics:
* The prolonged use of cannabis does not lead to the development of
physical dependence. There is minimal development of tolerance to
cannabis products(11,13,14,24)
* Cannabis products have exceedingly low toxicity(24,9,21,22,23) (The
oral dose required to kill a mouse has been found to be about 40,000
times the dose required to produce typical symptoms of intoxication in
man.)(21,24)
* Cannabis produces no disturbance of vegetative functioning, whereas
the opiates inhibit the gastro-intestinal tract, the flow of bile and
the cough reflex.(12,24,44,46,25)
Psychic Effects
Besides investigating the physical effects of medicinal preparations of
cannabis, nineteenth-century physicians observed the psychic effects of
the drug in its therapeutic applications. They found that cannabis first
mildly stimulates and then sedates the higher centres of the brain.
Hare suggested in 1887 a possible mechanism of cannabis' analgesic
properties:
During the time that this remarkable drug is relieving pain a very
curious psychical condition manifests itself; namely, that the
diminution of the pain seems to be due to its fading away in the
distance, so that the pain becomes less and less, just as the pain in a
delicate ear would grow less and less as a beaten drum was carried
farther and farther out of the range of hearing.
This condition is probably associated with the other well-known symptom
produced by the drug; namely, the prolongation of time.(16,26)
Reynolds stressed the necessity of titrating the dose of each patient,
increasing gradually every third or fourth day, to avoid 'toxic'
effects:
The dose should be given in minimum quantity, repeated in not less than
four or six hours, and gradually increased by one drop every third or
fourth day, until either relief is or the drug is proved, in such case,
to be useless. With these precautions I have never met with any toxic
effects, and have rarely failed to find, after a comparatively short
time, either the value or the uselessness of the drug.(22)
Synthetic Drugs Take Over
The unchallenged position of cannabis as the remedy of choice in cases
of migraine was recognised in 1916 by its inclusion in Osler's standard
textbook.(27) The flurry of papers in the medical journals, particularly
notable in the 1880s and 1890s, died away as cannabis took its place as
a routine prescription for many conditions. By this time, however,
there was increasing competition from new synthetic drugs, and the
extensive use of cannabis was coming to be the mark of a rather
conservative, and probably elderly doctor. According to Walton:
This popularity of the hemp drugs can be attributed partly to the fact
that they were introduced before the synthetic hypnotics and analgesics.
Chloral hydrate was not introduced until 1869 and was followed in the
next thirty years by paraldehyde, sulfonal and the barbitals. Antipyrine
and acetanilide, the first of their particular group of analgesics,
were introduced about 1884. For general sedative and analgesic purposes,
the only drugs commonly used at this time were the morphine
derivatives, and their disadvantages were very well known. In fact, the
most attractive feature of the hemp narcotics was probably the fact that
they did not exhibit certain of the notorious disadvantages of the
opiates. The hemp narcotics do not constipate at all, they more often
increase than decrease appetite, they do not particularly depress the
respiratory center even in large doses, they rarely or never cause
pruritis or cutaneous eruptions and, most important, the liability of
developing addiction is very much less than with opiates.(44)
Cannabis Under Attack
The addiction liability of the opiates had been dramatically increased
by the introduction in the 1850s of the hypodermic syringe, which
enabled water-soluble drugs to be administered intravenously, with
virtually instantaneous effect. The fact that cannabis, being
non-soluble, could not be administered in this new, more 'scientific'
way was doubtless held against it by some members of the medical
profession, as indeed it still is today.
By the 1930s, when the scare campaigns against marihuana smoking by
Mexicans in the New Orleans area and elsewhere were beginning to get
under way,(28) cannabis was regarded among the medical profession as an
obscure and unexciting traditional drug on which little original
research had been done for more than thirty years and which was
notoriously variable both in composition and in effect. Furthermore, the
intoxication occasionally seen with medicinal doses, which was well
recognised by the nineteenth century practitioners, who invariably
pointed out that it was quite harmless(20,22), was now looked at in
quite a different light in view of the increasingly lurid reputation
attached to recreational cannabis use, which was being described at this
time as the major cause of insanity in both India and Egypt.(29)
However, when international control of the cannabis traffic was
established under the terms of the Geneva Convention of 1925 the
continuation of its medical use was provided for. During the 1930s
cannabis continued to be found as a constituent of many proprietary
medicines(30), of which Chlorodyne became the best known. However,
cannabis was never a major source of income for the pharmaceutical
companies; the semisynthetic derivatives, such as Cannabin, which was
first marketed in the 1890s(31), never replaced the natural extract and
tincture, on which profits were inevitably much lower than on synthetic
drugs. American-grown cannabis was introduced onto the US pharmaceutical
market in 1918 in competition with the Indian product, which was
heavily taxed.(32) In spite of the enactment of prohibitory legislation
in many states, the American Medical Association continued to defend the
medicinal use of cannabis:
... there is positively no evidence to indicate the abuse of cannabis as
a medicinal agent or to show that its medicinal use is leading to the
development of cannabis addiction. Cannabis at the present time is
slightly used for medicinal purposes, but it would seem worthwhile to
maintain its status as a medicinal agent for such purposes as it now
has. There is a possibility that a re-study of the drug by modern means
may show other advantages to be derived from its medicinal use.(33)
The AMA vigorously opposed the passage of the Marihuana Tax Act of
1937(34), arguing that it would make the continued therapeutic use of
cannabis impossibly difficult. Their forebodings soon proved correct. In
1941 cannabis was dropped from the US National Formulary: the Federal
Bureau of Narcotics subsequently was able to eliminate therapeutic use
by the simple expedient of refusing any licences for the manufacture of
cannabis preparations, after which the only legal source of the drug for
any purpose was the Bureau itself.(35)
The Chemistry of Cannabis
Outside the USA the medicinal use of cannabis continued to be legally
possible, although increasingly rare. Surprisingly, the ten years
following the Marihuana Tax Act saw an upsurge of cannabis research for
the first time since the 1890s. Little of this was directed towards
therapeutic uses, although the 1940s saw major advances in understanding
the chemistry of cannabis as a result of the work of Adams in
Chicago(36) and of Todd at Cambridge(37). Adams and his group proceeded
to develop synthetic homologs and analogs of the natural cannabis
constituents which were up to 500 times as strong, as measured by animal
tests.(38) The subsequent history of research on these compounds is
interesting. The last published paper, in 1950, was a brilliant study of
11 different THC homologs for potency, analgesia, anticonvulsant
activity, and hypnotic qualities. More than twenty years of silence
followed. In fact the work continued, under US Army auspices, at
Edgewood Arsenal, Maryland and through sub-contractors Arthur D. Little
and Co. and the University of Michigan, the purpose now being the
production of effective 'incapacitating agents' for chemical warfare
purposes. In the event, nothing of military interest resulted; the
existence of this research was revealed in 1967(39) and the results were
declassified in 1971(40). As well as confirming the anticonvulsant
activity first reported by O'Shaughnessy, suggesting that cannabis might
be a potent anti-epileptic, this research also showed THC homologs to
be powerful hypothermogenic agents, producing a reduction in body
temperature which could be valuable as an adjunct to surgery.(41)
Research in the Forties and Fifties
To return to the 1940s, the other main research effort of those years
was commissioned by Mayor La Guardia of New York.(42) Publication of the
results aroused much controversy, since the report dismissed many of
the supposed ill-effects of marihuana smoking which had been generally
accepted up to that time. The Journal of the AMA, which had always
consistently supported the therapeutic use of cannabis(43), now reversed
its position and, in the course of a violent attack on the report,
supported such critics as Commissioner Anslinger by describing the
treatment of opiate addiction with cannabis as 'the substitution of one
addiction for another.'(44) The Journal has maintained a strongly
anti-cannabis stance from that day to this.
Between 1945 and 1956 such therapeutic research as there was (which was
very little) concentrated on psychiatric uses, primarily in the
treatment of depression. Although some spectacular successes were
seen(45), the results taken as a whole seemed unpromising(46). By this
time research with cannabis in the USA was no longer encouraged, and all
the American workers in this field used Adams' synthetics.
Interestingly, it was the two programmes in which real cannabis was used
(Rolls and De Groot) which produced some of the best results; but by
this time it was of course LSD which was the favoured drug for work of
this kind.
It seems quite likely that the work of Rolls and Stafford-Clarke in 1953
(with one patient) was the only use of the therapeutic potential of
cannabis by the medical profession anywhere in the 'developed' world
between 1942 and the 1960s. The low point was reached in 1956; in the
same year as the US Congress passed the Boggs Act, introducing 20 year
minimum sentences for cannabis offences, the United Nations decided to
take the opportunity of the forthcoming conference to draft a 'single
convention' on international drug control to recommend the complete
abolition of the medical and quasi-medical use of cannabis throughout
the world. No sooner had this decision been made than the bureaucrats
were thrown into a flurry by the appearance of a very detailed report
from Czechoslovakia which suggested that cannabis might have a
completely new therapeutic application—as an antibiotic(47). This was
entirely unexpected, although it is possible in retrospect to see that
the nineteenth century reports of cannabis as a cure for gonorrhoea
might not be so silly as they had seemed for so long.(48)
Antibiotic Effects Ignored
The Czech team established without any possibility of doubt that
extracts of hemp grown in Czechoslovakia had bactericidal properties.
They further succeeded in isolating the substance mainly responsible for
this activity (cannabidiolic acid), although they also noted that the
extract itself was more effective than any single constituent.(49) It
was effective , against Staphylococcus, Streptococcus, Pneumococcus, and
many other Gram positive bacteria. It was inactivated by blood serum
and was therefore useful only for external use(50). It was, however,
found superior to penicillin in the treatment of sinusitis(51), used
successfully on a large scale in dentistry(52), applied in the treatment
of ear infections(53), and used to achieve complete cure of an infected
thumb which had been threatened with amputation after the failure of
standard antibiotics(54). This work, however, was not too difficult to
ignore, especially since most of it was never translated from the
Czech.(55) The World Health Organisation had committed itself in 1952 to
the flat statement that "there is no justification for the medical use
of cannabis preparations."(56) In 1955 they recommended "extension of
the effort towards the abolition of cannabis from all legitimate medical
practice"(57), and in the same year was "pleased to note the decision .
. . to place cannabis drugs . . . together with heroin and
ketobemidone, in . . . Schedule IV . . . in the . . . Single
Convention"(58) (which in the draft convention involved the prohibition
of medical use.) It was not until 1961 that the Czech work was reviewed
in detail.(59) The resulting report laid great stress on the fact that,
six years after first publication, there was still no product on the
market (although in view of the international legal climate this was
hardly surprising), as well as on the existence of other antibiotics
(particularly neomycin and bacitracin) which could duplicate the effects
obtained with cannabis.
Although unbiased medical opinion might have take the view that a new
antibiotic, even if limited in its applications, would be a useful thing
to have, the WHO group "concluded that at present the case has not been
proved in favour of making cannabis resin available for the extraction
of drugs. The opinion expressed in our third report (in 1952) remains
unchanged. Cannabis and its preparations are practically obsolete, and
there is no justification for their medical use."(60) The Czechs seem to
have accepted their defeat; a few years later their team's leading
chemist turned to applying his talents to the development of new
analytical techniques for use by law-enforcement agencies(61).
"A Thoroughly Vicious Drug"
In spite of having so easily disposed of the Czechs, the UN master plan
for world-wide cannabis prohibition came to grief after all. It was
defeated by the opposition of the British government, which had been
defeated on this issue in 1956, to any attempt to prohibit the medical
use of heroin, as well as the determined opposition of the governments
of India and Pakistan to any measure which would deprive their people of
the only type of medical care available to many of them. The Indian
representative referred pointedly to the need for underdeveloped
countries to make use of their natural resources (instead, presumably,
of importing expensive pharmaceuticals from the West)(62). The result
was a complicated compromise. The new convention(63), signed in 1961,
provided that the prohibition of medical use of Schedule IV drugs
(including cannabis and heroin) should be merely recommended, rather
than obligatory. Extracts and tinctures of cannabis were placed in
Schedule I, so that this recommendation did not apply to them, and the
'quasi-medical' or 'traditional' use of cannabis in India and Pakistan
was to be phased out over 25 years.
In spite of the compromises they had had to make, the framers of the
Single Convention could be reasonably sure that the medical use of
cannabis was on its way out at last. The signatories of the Convention
effectively endorsed the view of cannabis which had established itself
since the 1930s; that "it is in fact a thoroughly vicious and dangerous
thing of no value whatever to humanity, and deserving of nothing but the
odium and contempt of civilised people."(64)
Influence of Increased Recreational Use
No sooner had this victory been won than the whole situation was
radically changed by the explosive growth of recreational cannabis use
throughout North America and western Europe, and soon all over the
world. It should be remembered that up to this time cannabis smoking
had, at least according to official figures, been on the decline for
more than half a century and an early end to it was confidently looked
forward to. In the new situation, in which the harmfulness or otherwise
of cannabis had suddenly become a political issue, the possible medical
uses began to be looked at again. In England, in the 1960s, extracts and
tinctures of cannabis could still legally be prescribed, and some
doctors began to show an interest in using them in the treatment of
alcoholism and addiction, as they had been used in the nineteenth
century. Some doctors, also, were inclined to regard relief of the
paranoia induced by fear of being arrested as a reasonable ground for
prescribing them to those who would otherwise smoke illegally obtained
cannabis. The Wootton Committee, in the course of their study of the
cannabis situation, were impressed by the therapeutic potential of the
drug and recommended that the power of doctors to prescribe it in the
ordinary way should be retained(65). In the event, it lasted only until
1973, when new legislation came into force which required medical use of
any cannabis preparation to be licensed.
New Research
The increase of cannabis use was followed by an increase in cannabis
research, the first result of which was the successful isolation of a
considerable number of cannabis constituents. As in the 1940s the
irrational belief that research on pure chemicals was somehow more
'scientific' immediately diverted most cannabis researchers to working
with THC. As interest in Cannabis Plantpossible new pharmaceuticals
derived from cannabinoids began hesitatingly to develop, the revival of
medical use of cannabis itself seemed, in the late 1960s, to be more
unlikely than ever. The discovery which was completely to change the
situation was made, like many important scientific discoveries, entirely
by accident. In 1971, in the course of a study of the effects of
cannabis on driving, it was observed that the smoking of cannabis lowers
intraocular pressure(66). The application of this effect to the
treatment of glaucoma, which many sufferers from that condition had had
to discover for themselves, was now something which medicine could no
longer ignore.
The 1970s saw the discovery or rediscovery of a whole range of
therapeutic possibilities for cannabis, hampered throughout by a
bitterly fought rearguard action by those who clung to the received view
that 'cannabis has no medical uses.' In the USA cannabis and its
derivatives were officially classified as 'investigational new drugs',
thus requiring the consent of a multitude of regulatory bodies to any
research; this classification simply ignored the whole mass of
scientific and medical data accumulated over more than a century and
required researchers to begin again from the beginning as if it had
never existed(67). The initiatives which led to the investigation of the
therapeutic possibilities of cannabis in cases of glaucoma, cancer
chemotherapy, epilepsy and spasticity in the 1970s came not from the
government or the medical profession but from individual sufferers from
these conditions who discovered beneficial effects for themselves.(68)
Current Therapeutic Uses(69): Glaucoma
There is now no doubt that the cannabinoids produce reduced intraocular
pressure. This effect is seen with cannabis, with THC, with THC
metabolites and with synthetic THC analogs, and with administration
intravenously, topically, orally or by smoking.(70) It seems, however,
that the THC eyedrop currently being tested is less effective than
smoked cannabis.(71) The application of cannabis to the treatment of
glaucoma was described in Hepler's original 1971 paper as 'obvious', and
in view of the fact that this disease is responsible for 14 per cent of
all cases of blindness its application might have been expected to be
treated as a priority. Nothing of the sort occurred, and glaucoma
patients were left, as they still are, to obtain supplies illicitly. In
1975 Bob Randall, who had been treating himself in this way for three
years, was charged with unlawful possession of marihuana and acquitted
on the basis of the common-law defence of 'necessity'. He was then
allowed to enroll as a volunteer in a research programme, as 'a
politically acceptable way of supplying me with marihuana,' as he put
it. In 1978, after his supply was interrupted, he brought proceedings
for an injunction against the federal government agencies concerned,
which were settled on the basis that cannabis from government sources
would in future be prescribed to him within the framework of the normal
doctor-patient-pharmacist relationship. He remains the only person in
the USA to be supplied cannabis legally other than for research
purposes.(72) According to the National Institute on Drug Abuse 'the
long-term safety and efficacy of marihuana-related drugs administered
chronically to glaucoma patients has not been established, nor is there
any data from long-term controlled studies to demonstrate whether these
preparations can actually preserve visual function in such
individuals.'(73)
Cancer Therapy
The second established modern therapeutic application for cannabis is as
an adjunct to cancer chemotherapy. The drugs used in cancer, treatment
produce severe nausea and vomiting; sometimes so severe that patients
are unable to continue with the only treatment which may save their
lives. Various anti-emetic drugs are commonly given in an attempt to
control this reaction: it now seems that cannabis is successful in a
substantial number of cases in which standard anti-emetics are
ineffective.(74) According to NIDA this "is probably the single most
promising application of these drugs."(75) Again, it is being used by
many patients, often on medical recommendation(76), from illicit sources
and illegally, while legal supplies are, confined to research purposes.
It also seems likely that cannabis may be effective in reducing muscular
spasticity in cases of multiple sclerosis. Although formal research is
at a very preliminary stage this again arises from reports from patients
who have used it on a do-it-yourself basis and found it effective.(77)
Prospects and Possibilities
There are a number of other possible therapeutic applications, suggested
by nineteenth-century uses, modern research on animals, or both. Some
are currently receiving research attention, but a number unfortunately,
are not.
1. Antiepileptic. This was an area of nineteenth century interest,
although findings were never entirely consistent(7,18,22,78). A very
brief research report of 1949 found a synthetic cannabinoid more
effective than a standard anticonvulsant in a group of epileptic
children.(79) Both THC and CBD (which is a natural cannabinoid without
psychoactivity) have been shown to have anticonvulsant effects in
animals, and favourable preliminary results have also been obtained in
humans with CBD.(80) A study of social cannabis-smoking among epileptics
failed to find any effect, whether adverse or beneficial.(81)
2. Gastrointestinal effects. Appetite stimulation is one of the best
known effects of cannabis, and the drug was often prescribed for this
purpose in the nineteenth century(7,8). One of the unsung research
triumphs of the 1970s was solemnly to 'confirm' this piece of common
knowledge by establishing that under controlled laboratory conditions
"subjects given 0.5 mg./kg. orally drank a greater quantity of a
chocolate milkshake preparation compared to those receiving
placebo."(82) This effect has recently been applied in the treatment of
anorexia nervosa, with some degree of success.(83) In addition to the
now well-known antiemetic effect the cannabinoids have a antidiarrhoeal
effect, at least in animals.(82) One or other of these effects, or both,
may explain the success achieved in treating indigestion and dyspepsia
in the 1890s(l7), as well as stomach ulcers, for which cannabis appears
to have been given at Guy's Hospital during the 1940s.(84) After many
years' neglect it has recently been shown that cannabis appears to
produce significant lowering of stomach acidity; this has led to the
suggestion that cannabis consumption may have been a major factor in the
substantial reduction of the incidence of stomach ulcers which has been
observed in a number of western countries in recent years. More work in
this field seems overdue.
3. Anti-asthmatic. Cannabis smoking undoubtedly causes acute
bronchodilation, with beneficial results in asthma attacks, although
chronic heavy smoking can produce the opposite effect as a result of the
irritant effect of the smoke.(82) Thus another traditional use,
well-established in the nineteenth century(78), is confirmed by modern
research. Work on aerosol preparations is under way.(85)
4. Sedative/Analgesic. The older work(7,8,18,21,22,26,78) suggests that
cannabis, in addition to its sedative action, has a specific
pain-relieving effect. This has been confirmed by modern research on
animals, in which cannabinoids have produced effects comparable to
morphine, and in cancer and surgery patients. It also seems that they
have value in combatting fever and inflammation(82) as suggested by U.S.
Defense Department studies.(40)
5. Treatment of Addiction. The older work on alcohol and opiate
withdrawal and substitution(15,18,21,42) has been followed up to some
slight extent. Although the history of substitution therapies in opiate
addiction is not encouraging, recent animal work does suggest that THC
can inhibit the morphine abstinence syndrome in animals(82). With
alcoholics synthetic cannabinoids(86), cannabis tincture(87) and
illicitly obtained cannabis(88) have all been used with some success.
6. Anti-depressant. Since the 1950s(45,46) there has been only one study
using THC, which was not encouraging(89). More work in this area may
still be justified(82).
7. Migraine/Headache/Neuralgia. In this area, where cannabis was once
the standard treatment(27), there seems to have been no modern follow up
at all.
8. Cough suppressant. The nineteenth century observations(8,26) have been confirmed in modern animal studies(90).
9. Menstrual Abnormalities. Confirmation of the once well-known results
in this field(10,12) has been rendered impossible by the prohibition in
the USA of all cannabis research on women of childbearing age. There is
however one modern observation which confirms the effect to some extent;
it seems that the menstrual irregularity induced by heroin use is less
marked in women who also use cannabis(91). Recent, as yet unpublished,
preliminary findings on a study of female cannabis users in New York
indicate that cannabis does indeed affect the menstrual cycle, possibly
producing a reduction in fertility. In accordance with the modern
tradition of cannabis research this is now interpreted as an adverse
effect on health rather than a possible therapeutic application.
10. Childbirth. The use of cannabis in childbirth is traditional in
Southern Africa and elsewhere(92). The sedative and analgesic effects
are clearly relevant; it has also been suggested that uterine
contractions are directly stimulated(93).
11. Antibiotic. There has been no follow-up on the Czech results(49-61) since 1965(94).
12. Antihypertensive. The use of cannabis in treatment of high blood
pressure has been suggested; the effect is related to that on
intraoccular pressure(82,95).
13. Anaesthesia. Cannabis is a sedative and potentiates the action of a
number of anaesthetics, suggesting a possible application in
premedication(82).
14. Cancer treatment. Apart from the well-established use in connection
with chemotherapy, and the possible use as an analgesic, both discussed
above, there is a rather speculative possibility that the direct
anti-tumour effect of some of the cannabinoids may be clinically
useful(82).
Where do we go from here?
From the above description of the present state of knowledge a number of questions suggest themselves, namely:
* Why is there such determined resistance to the provision of cannabis drugs for therapeutic purposes?
* Why is there such pressure in favour of the use of synthetics or THC
rather than natural cannabis, to the extent that researchers who wish to
use the latter are forced to use the former instead?
* Why is nothing happening anywhere outside the USA?
In relation to the first two questions the fundamental problem is the
irrational insistence that cannabis is a new drug in the same sense that
a substance synthesised yesterday in the laboratory of a pharmaceutical
company is a new drug. The only possible basis for this approach is
that the legal classification of the drug as having no therapeutic use
outweighs three thousand years of experience to the contrary. A great
deal follows from this classification, for all countries require new
drugs to undergo extensive tests before they are allowed to be put on
the market; in the USA these tests are particularly stringent and
invariably take several years and cost several million dollars.
There is nothing unreasonable about this in the case of a genuinely new
drug; the pharmaceutical company which develops the drug will finance
the tests and recoup the cost out of profits on subsequent sales. The
synthetic cannabinoid analogs are certainly new drugs and no-one denies
that this procedure should be applied to them; the delay before the drug
is made available for therapeutic use is the price which must be paid
for ensuring the safety of the product. In the case of cannabis itself,
however, two factors completely change the situation; the first is that
the drug has already been tested far more thoroughly than any
pharmaceutical by several hundred million willing, indeed enthusiastic,
volunteers; the second is that cannabis, being a natural product, is not
patentable, and hence there is no incentive to any company to spend its
funds on the necessary work.
In reality the 'new drug' classification of cannabis fulfils one purpose
and one purpose only; protection for the pharmaceutical industry, which
is devoting a great deal of effort to the synthetics, against the risk
of having to compete with a natural product which could otherwise be on
the therapeutic market before their own much more expensive and much
more profitable preparations are ready(96). The other effect of this
policy is that large numbers of cancer and glaucoma patients are left
without legal access to a substance which can certainly benefit them and
possibly save their eyesight or their lives and which is simultaneously
being used by millions of people for pleasure and is available on any
street corner. In these circumstances it is hardly surprising that a
fair number of reputable physicians have felt that they had no
alternative to advising their patients of the possible benefits and
leaving them to obtain their own (illegal) supplies. Guides have even
been published to how best to use material obtained in this way(76).
The lunacy of this situation has led to a widespread revolt against the
official line, ably co-ordinated by the U S. National Organisation for
Reform of Marihuana Laws. Twenty-four states have now passed special
legislation to make cannabis available for therapeutic purposes, in
disregard of the categories established by federal law, although
difficulties are still encountered where supplies must be obtained from
federal agencies(97).
The reason for the lack of action outside the USA has been simply that
cannabis research of any kind is now almost entirely an American
preserve. Therapeutic effects have been discovered or rediscovered
entirely as an unintended (and to some unwelcome) spin-off of a 35
million dollar research programme designed primarily to identify the
deleterious effects of recreational cannabis use(98), and which came
into existence in response to public pressures for cannabis law reform.
The extensive results of this programme are now, of course, available to
be applied anywhere, although it is remarkable to see that in the UK
even the basic research which is needed to allow the American
information on cannabis and health to be applied to the British
situation has not been done(99). The only British therapeutic research
yet published consists of work on the use of THC as a sedative in lung
cancer patients and a study of the bronchodilator effects of cannabis
extract, both carried out at the Welsh National School of Medicine.
There are currently seven researchers holding Home Office licenses in
this field, of whom six are working on cancer chemotherapy and one on
glaucoma(100). These research workers are apparently expected to
maintain a low profile; their names and affiliations are not available.
It does not seem that anyone wishes to be known to be working with such a
disreputable substance and the less publicity these licenses get the
less likely it is that more doctors will apply for them.
All these researchers are working with THC; there appears to he no
official source of natural cannabis for therapeutic research in the UK.
However, now that the therapeutic possibilities of cannabis have been
forcibly placed before the British medical profession(101) it may be
that action will follow. For the sake of the patients involved it is
certainly to be hoped that it will. Since it is only seven years since a
British pharmaceutical company was distributing extract and tincture of
cannabis to pharmacies for supply on prescription it is hardly possible
that it could be regarded as a 'new drug' here.
Lessons to be Learnt
What lessons are to be learned from the tangled history of cannabis as a
medicine? The first and most impressive is how sheer prejudice and
superstition can lead to the total abandonment (as seen in the 1950s) of
medicinal use and even of medical research into what was once a
therapeutic substance of major importance. The second is how rapidly
experience of its use even in the very recent past can be denied or
forgotten; in the case of extract and tincture of cannabis in the UK
this occurred while the substances were still available in pharmacies
and listed in the pharmacopoeia and indeed after some of the new
research results of the 1970s, such as those on glaucoma, were already
available. The third, and in some ways the most interesting, lesson is
how much modern researchers could learn from their nineteenth-century
counterparts. Traditionally, before a researcher tested a drug on
humans, he tried it on himself(102). This excellent tradition has quite
recently been abandoned by those labouring under the illusion that
subjective observations are 'unscientific' a view which has no support
from any reasonable theory of scientific methodology. It is remarkably
easy to distinguish between cannabis research done by those with
personal experience of the drug and that done by those without, and to
see how the first group have been assisted, at least to the point of
knowing what are relevant questions to ask, while the second have been
hindered by their ignorance. Insights derived in this way must of course
be submitted to objective testing: but until the right questions are
asked all the objective research in the world will produce no results of
any value. A great deal of information on cannabis is available from
the subjective experience of its users; it is tragic that so little use
is made of it. This is particularly important now that the
'psychoactive' or intoxicant properties of cannabis are increasingly
being seen by medical researchers as an undesirable side-effect.
Cannabis 'intoxication' is, of course, a learned effect; the importance
of this in the context of therapeutic use has been discussed in a
characteristically discursive and insightful paper by Prof.
N.E.Zinberg(83).
The modern pharmacologist's attitude has been expressed by Prof. R.
Mechoulam in these words: "The main problem facing pharmaceutical
research into cannabis is not the lack of activity but rather the wide
spectrum of activity exhibited by the cannabinoids. In the clinic, one
needs drugs which are specific for a certain condition and do not cause
other effects."(103) While the process of torturing molecular
configurations until they respond to human preconceptions about what a
drug ought to do goes on apace, it may still be worth pleading for a
little more investigation of the complex mixture of cannabinoids which
nature has provided us with, in the form of a plant which has been
associated with humanity since before the dawn of recorded history.
Scientists working in the UK have revealed that cannabis has the potential to destroy leukemia cells.
THC
is the acronym of delta-9-tetrahydrocannabinol, and is is the main
psychoactive substance found in the cannabis plant. For the plant
itself, the THC is a natural method of protecting itself from pathogenic
agents or herbivores animals. It also offers a really good protection
against the sun's UVB rays. Men have grown cannabis for thousands of
years to extract the THC out of it. As you may have noticed, we show
the THC level for most of the strains in our catalog. We need to specify
something about this information. Every strain, every single seed have a
potential. It's up to the grower then, if the potential will be fully
released or not. If you read that a strain have 10% of THC, rating it
doesn't mean that every plant of that strain will have 10% of THC. It
mean instead that that strain have a potential of producing about 10% in
THC. In the hands of an expert, in the right conditions, these seeds
will produce 10% or even more. In a less favorable environment, the same
seeds will produce for example 8%. All these words are a reminder that a
seed is not a computer, where the values are only 0 and 1. It's a live
creature and the final result will be the combination of thousands of
little variables. We proudly say that we can offer you the best
potential there is, but we can never guarantee (and nobody can) that you
will always achieve the values in the description.