CANNABIS :
OUR POSITION FOR A CANADIAN PUBLIC POLICY
REPORT OF THE SENATE SPECIAL COMMITTEE ON ILLEGAL DRUGS
VOLUME I : PARTS I and II
Part
II
Cannabis:
effects, types of use, attitudes
Chapter 5
Cannabis:
From Plant to Joint
Cannabis,
marijuana, pot, grass, kif, grifa, ganja–from so many cultures, so many names
for the drug made from cannabis sativa
indica, one of the two main varieties of hemp. Beyond these various names
are also different ways in which the drug is used and the context of those
various usages: here marijuana is rolled with cigarette tobacco in a cigarette
paper (joint), there kif is smoked in a pipe and elsewhere ganja
is smoked in a water pipe. Sometimes it is baked into cookies or cakes. The
French pétard, the English joint or
the Indian bangh are all names for the
product consumed and, at the same time designate different usages: marijuana is
most often composed of the plant's flowering tops and dried, powdered leaves; sinsemilla
is a preparation consisting of female tops of a private variety of seeds,
whereas Indian ganja consists solely of fertilized flowering tops.[1]
These
names are not mere accidents of folklore: like other substances, cannabis has
codified uses that vary across cultures. The words used to name the same drug
refer to a set of relations that populations of various cultures maintain with
it, a kind of code of manners, but also of reasons to use the drug. In North
America (United States and Canada), marijuana has long been identified with
youth and the sexual liberation of the 1960s; in India and Jamaica, ganja
has religious aspects which it does not necessarily possess in the West; and
this same drug has still other cultural meanings in the Maghreb. We return to
this question in Chapter 6.
This
chapter first describes the cannabis plant and the various forms in which it
becomes a consumer drug. We then take a brief look at the geographical origin of
the cannabis plant and the routes along which it circulates in the modern world,
noting at the same time its current modes of production (soil‑based and
hydroponic) which have developed in certain regions of Canada. We then describe
the pharmacokinetics of the cannabis plant, in particular its main active
ingredients and their metabolism in the body.
One
plant, various drugs[2]
There
are a number of varieties of cannabis. The best known are Cannabis
sativa, Cannabis indica and Cannabis
ruderalis. Cannabis sativa is the
main variety which grows in virtually any climate. In dry, sandy and slightly
alkaline soils, it yields plants that can reach up to seven meters in
height. In Canada, the preferred variety for soil‑based cultivation is Cannabis
indica, which is a shorter plant, but with higher concentrations of D9‑THC
(the main active ingredient of cannabis, discussed more fully below). There are
male and female plants. In general, female plants are richer in D9‑THC
than the males, which are often smaller and bare of leaves. D9‑THC
is mainly found in the resin secreted by the flowering tops.
Flowering tops and leaves of
cannabis
It
appears that cannabis was first known in China some 6,000 years ago, then
subsequently in India, then the Middle East, Africa, Mexico and South America.
Cannabis can be cultivated in a number of ways, in greenhouses or
hydroponically, which makes it possible to increase plant productivity and
achieve high D9‑THC
levels. Methods for genetically selecting the best greenhouse varieties and
crops have also made it possible to increase the active ingredient content.
Male
and female cannabis plants
Marijuana,
which is a Mexican term initially used in reference to cheap tobacco, but which
subsequently designated certain parts of the cannabis plant, is generally green
or brown in colour and produces a characteristic odour when burned. It resembles
oregano or coarse tea.[3]
Marijuana comes from all the parts of the plant once dried. In this form, its
THC content is lower; THC content is increased by selecting the flowering tops
of the female plant. Dried and coarsely powdered, marijuana is most often rolled
into thin cigarettes together with cigarette tobacco (joint), and sometimes
smoked in a pipe or, less frequently, in cigar form. A typical joint contains
between 0.5 and 1 g of cannabis. Like hash, it can also be baked into
cookies and cakes, and be drunk as an herbal tea as well. A number of
specialists told us that domestic cannabis made through controlled greenhouse
production costs approximately $100 an ounce, and is then sold on the street at
average prices ranging between $200 and $250. While we consider this estimated
production cost high, the only other available studies concern production costs
in developing countries such as Morocco.
Marijuana
and joints
Hashish,
also known as hash, shit, kif (in North Africa) and charas
(in India), is the viscous resin produced by the marijuana plant and obtained by
pounding then compressing the dried leaves and flowering tops to obtain what, in
France, is called a "barrette" or here a cube or block. It takes
approximately 45 to 75 kg of cannabis to produce 1 kg of hash, which
is sold in light brown to black pieces of hard or soft consistency. It is
frequently smoked, alone or mixed with tobacco or marijuana, in a cigarette
(joint), pipe or, more rarely, cigar. It may also be baked into cookies or
cakes. The D9‑THC
content of hash is generally between 3% and 6% in normal production. As is the
case for cannabis, D9‑THC
content can be increased through growing methods and resin concentrations to
achieve levels of more than 10% on average. Slightly more expensive than
marijuana, hashish sells for approximately $300 to $350 an ounce on the street.
Haschich
There
are two other cannabis‑based products, marijuana and hashish oils, which
are extracted from resin using 90‑proof alcohol, which is subsequently
evaporated through exposure to the sun. These oils are viscous, greenish brown
to blackish, foul‑smelling liquids, with generally higher cannabinoid
concentrations of up to 30% to 60% D9‑THC.
Oils are generally dripped onto cigarette paper or tobacco then smoked. They are
scarce and more expensive than other products.
Cannabis
oils
The
following passage from a report prepared by Labrousse and Romero for the Observatoire
français des drogues et des toxicomanies (OFDT; French Monitoring Centre
for Drugs and Drug Addictions) in 2001 on cannabis production in Morocco
describes the various stages of production very clearly.
Cannabis roads
Where
does the cannabis and hashish available in Canada come from? What quantities are
imported and how much is produced locally? What routes are used to transport the
drugs between provinces? What quantities are exported to other countries? What
is the monetary value of this market? These are constantly recurring questions.
They serve various purposes: to underline the scope of the drug “problem”
generally, to explain the power of organized crime which makes money from drugs,
as well as to substantiate the discrepancy between the size of the problem and
the limited resources governments allocated to reducing supply. But this
information can also assist in better understanding the extent of the problem
experienced by peasants in the various producer countries, the ecological issues
raised by the cultivation of drugs, as well as the strategic position of drugs
in geopolitics.
The
cultivation of cannabis is the most widespread of all illegal drugs, which is
not surprising since, not only does the plant grow readily in a number of
climates, but it also requires little processing before becoming marijuana.
According to the 2000 report of the United
Nations Drug Control Program (UNDCP):
Over
the last decade, 120 countries reported illicit cultivation of cannabis in
their territory. Interpol identifies 67 source countries for cannabis
through seizures made in 1998. (…) Estimating the extent of illicit cannabis
cultivation, production and trafficking is much more difficult than for other
plant‑based drugs because of the significant amount of wild cannabis
growth, the diverse nature of cultivation and the sheer magnitude of
trafficking. In contrast to other plant‑based narcotic drugs, illicit
cannabis products can originate from three qualitatively distinct sources of
supply: outdoor illicit cultivation; naturalized cannabis plant populations
(wild growing cannabis); and plants cultivated indoors by means of sophisticated
growing technology. (…) The large number of countries reporting an increase in
cannabis consumption (two‑thirds of all countries reporting drug abuse
trends in 1996) would suggest that overall production must have increased; but
this is only partly confirmed by seizure data. (…) Cultivation estimated
(including wild growth), based on reports from Member States in the 1990s,
ranges from 670,000 hectares to 1,850,000 hectares. Production
estimates vary by a factor of 30, from 10,000 tonnes to 300,000 tonnes.
Linking production and consumption estimates, UNDCP estimates world wide
cannabis production to be at about 30,000 tonnes. [4]
As may be seen, estimates vary greatly and are enormously difficult to
validate. How can anyone estimate the number of cannabis plants that are
transformed into marijuana? The data provided by the governments of various
countries on cultivated areas are themselves only approximations. As to the
number of greenhouses and other forms of production, there is quite literally no
way of knowing.
The work
of the team at France's Observatoire géopolitique
des drogues, under the direction of Alain Labrousse, is exemplary in
the field. The box from the same report produced for the OFDT in 2001,
describes a three‑month field project in which the authors
cross‑checked data from various sources.
In
particular, it has been observed that, when linked to the population of
potential cannabis users (which the Centre estimates at some 120 million
persons), the estimated global production of 30,000 tonnes is much nearer
the 10,000 tonne floor than the 300,000 tonne ceiling.
According
to the UNDCP, the main producers are Colombia and Mexico (marijuana) and Morocco
(hashish). According to the International Criminal Police Organization
(Interpol), Morocco, Afghanistan and Pakistan are the main sources of hashish
and Colombia, Niger and South Africa of cannabis. Lastly, according to
Labrousse, marijuana production is exploding, with Colombia becoming again the
major producer it was in the 1970s, and production rapidly increasing in West
Africa (Nigeria, Ghana, Congo, Ivory Coat, Senegal), although the great steppes
of the Commonwealth of Independent States (Kazakhstan, Kirghizistan, Ukraine,
Belarus and Azerbaijan) have virtually unlimited export potential, while
Afghanistan and Pakistan likely produce 2,000 tonnes of hashish, the
equivalent of Morocco's production.[5]
In addition, Canada has been a cannabis exporting country for a number of years
now.[6]
Traditionally,
the cannabis available in Canada comes mainly from Mexico, Jamaica and the
countries of the horn of Africa, while hashish originates mainly in Asia and the
Middle East:
The
hashish market in Central Eastern Canada is known world‑wide. U.S.
criminals are among the international traffickers who orchestrate
multi‑tonne shipments of this drug from Pakistan directly to Montreal by
mothership or container. In 2001, some shipments transited the United Arab
Emirates, Africa and Europe before reaching Canada. Multi‑kilo quantities
are also imported from Jamaica by couriers travelling on board commercial
airlines. [7]
While
a large portion of cannabis sold in the Canadian market was of foreign origin
until the 1980s, the situation has radically changed since that time. It is
estimated that national production has now supplanted imports. In its 1999
report, the Royal Canadian Mounted Police writes:
It
is estimated that more than 50% of the marihuana available in Canada is produced
domestically. Of the foreign marihuana seized in or en route to Canada in 1999,
at least 5,535 kilograms originated from Jamaica, 825 kilograms from
South Africa and 860 kilograms from Mexico. Foreign shipments arrive
directly into Canadian ports of entry or transit through the United States
before reaching Canada. On June 11, 1999, U.S. Customs intercepted 2,464 kg
of Jamaican marihuana and 141 kg of hash oil at Newark, New Jersey in a
marine container bound for Montreal. Furthermore in Project JOULE on June 20,
1999, 2,617 kg of Jamaican marihuana destined for Canada were seized in
Stuart, Florida. [8]
How much
cannabis and hashish are available in Canada? What is the monetary value of
those drugs? It is in fact impossible to answer these questions, for obvious
reasons, since the drugs are illegal. While we know the amount of tobacco
produced and sold in cigarette form, and the volume of alcohol produced or
imported and consumed, and sales turnover can be calculated in both cases on the
basis of those volumes, it is impossible to do this for illegal drugs.
For a
time, the United Nations International Drug Control Program suggested that the
total value of the illegal drug "industry" was approximately US $400 billion,
greater than the oil industry.[9]
The total value of cannabis obviously cannot be separated from that amount, even
though we know that the largest number of persons who use drugs use cannabis. No
one really knows how or on what basis these figures are advanced, whether they
were produced using a rigorous calculation method or merely noted down on a
napkin over a meal.[10]
And yet they often serve as a reference. In a series of articles published on
the illicit drug issue in 2001, The
Economist cited the $400 billion amount before suggesting a more
conservative estimate of US $150 billion.[11]
By comparison, the value of the pharmaceutical industry is near US $300 billion,
that of the tobacco industry $204 billion and that of the alcoholic
beverages industry $250 billion.
Since
the authors provide itemized accounts of their calculation methods, we will now
continue our analysis of the Moroccan example.
We know
of no similar field work for Canada or Mexico. In addition, in Canada, climatic
conditions have stimulated development of greenhouse and hydroponic crops, and
the ratio of these cultivation methods to soil cultivation methods is not known.
We
therefore use the following figures and data on cannabis production, cannabis
and hashish imports and the monetary value of those drugs in the Canadian
market, with considerable reservation and prudence.
According
to the RCMP, "the annual production
of marijuana in Canada [is] at least in the 800 tonne range. This estimate
appears overwhelming, however investigators believe it is quite conservative,
and it is supported by intelligence and seizures of marijuana in plant and bulk
forms."[12]
The same figures are stated in the 1998 and 2002 reports. Note as well that, at
800 tonnes, Canadian production represents approximately 2.5% of global
production, as stated by the UNDCP.
In its
1998‑1999 annual report, the Observatoire géopolitique des drogues stated
that, based on police sources, the value of the illegal drug market in Canada
was $7 billion to $10 billion a year.[13]
For 2001, the RCMP estimated that the market value of all illegal drugs was $18 billion.[14]
It is impossible to estimate the share of cannabis and hashish in that total. As
we most often do not know the calculation basis for these estimates, they must
also be prudently considered. As the Assistant Deputy Solicitor General stated
in his appearance before the Committee, the calculation methods, based on the
assumption that police and customs organizations seize 10% of all drugs, are
unscientific and unreliable.[15]
We nevertheless note an apparent inconsistency: the seeming stagnation of
cannabis production at 800 tonnes and of hashish imports at 100 tonnes
since 1998, as well as the declining prices of heroin and cocaine in a stable,
even declining market (RCMP reports) are not consistent with the presumed
doubling in total value of the drug market. As a result, in dealing with these
various estimates of the quantity of drugs produced and monetary value of the
drug market, the Committee often had the impression that, ultimately, no one
really knew how big it was.
With
regard to hashish, the RCMP believes that it
is
easier to estimate the quantity of hashish entering the Canadian market annually
than the quantity of any other illegal drug. Unlike what is observed for other
drugs, such as cocaine and marijuana, that can be found across Canada and the
United States, hashish use in North America is a localized phenomenon. The drug
is very popular in Quebec, Ontario and the Atlantic Provinces, whereas demand is
limited elsewhere in Canada and supply is sporadic at best in the northeastern
United States. Consequently, Montreal organized criminal groups are specialized
in the massive importing of hashish and have a monopoly on its distribution in
bulk. In view of these facts and of information on multi‑tonne hashish
shipments seized in Canada and abroad and on those we know have entered the
Canadian market, RCMP analysts estimate that at least 100 tonnes of the
drug are imported into Canada each year. [16]
Canada
is also an in-transit country for drugs to the United States, and a significant
portion of Canadian cannabis is intended for export, in particular to that
country.
Smuggling
of Canadian marihuana to the United States remains a source of concern for
enforcement officials on both sides of the border. Though this activity is
particularly noticeable on the British Columbia–U.S. border, it is not limited
to that province. There is intelligence that the Hell's Angels in Quebec are
supplying marihuana to their U.S. counterparts. Intelligence also indicates that
there is marihuana smuggling activity across the Great Lakes. Despite the
foregoing, few U.S. marihuana seizures can be traced back to Canada. [17]
In 1999,
Washington officials suggested that Canada could be placed on the list of
countries suspected of a soft stance in the fight against drug production and
trafficking. More recently, officials of the Drug Enforcement Administration
repeated that Canada's trafficking in cannabis toward the United States was a
significant problem. One RCMP officer told a national newspaper that
approximately 70% of marijuana grown in Canada wound up in the United States,[18]
whereas, according to the 2002 report of the International Drug Control Agency,
the figure was approximately 60%.[19]
We have heard, and RCMP officers confirmed it, that cannabis from British
Columbia has such a high value that it was traded on par with cocaine. According
to those police officers specialized in the war on drugs, British Columbia's
triple A quality cannabis is worth approximately $4,000 a pound in Canada and
one kilogram of cocaine is currently worth US $11,000. However, while
reference is made to this supposition in the annual report for 1999, it is not
confirmed:
Canadian
marihuana is sometimes used as a currency to purchase cocaine that is warehoused
in the U.S.A. The exchange ratio is about three to one. Exchanges of one to one
have been rumoured but never substantiated. Furthermore, such a rate of exchange
does not make sound commercial sense considering that a kilo of cocaine sells
for $13,000 U.S. (in lots of 50 kilos or more) while the wholesale price of
a kilo of marihuana ranges around $6,000 or $8,000 U.S. [20]
In its
2002 report, the RCMP merely mentions the fact that Canadian cannabis is
exchanged for cocaine, without saying whether it is on an equal weights basis.
We also note a certain inconsistency here as the price of a kilogram of cocaine
is expressed in US dollars, whereas that of a kilogram of marijuana is expressed
sometimes in Canadian dollars, at other times in US dollars.
British
Columbia, Ontario and Quebec are the main producers in Canada. British
Columbia's large production can be attributed in particular to suitable climatic
conditions, but there are probably also sociocultural explanations, as the
Pacific Coast mentality explains in part why cannabis appears to have taken root
there to a greater extent.
Cannabis
production in British Columbia appears to have increased significantly over the
past 10 years, becoming, according to some analysts, one of the province's
biggest industries in terms of monetary value, which some analysts set at $6 billion,
whereas, according to some police officers, a conservative estimate would be $4 billion.[21]
If marijuana sells for $225 an ounce, at 16 ounces a pound, British
Columbia would appear to produce the equivalent of 550 tonnes of cannabis a
year, more than two‑thirds of the total amount of cannabis circulating in
Canada.
Testifying
in Richmond, B.C., on 14 May 2002, RCMP Superintendent Clapham
said there were between 15,000 and 20,000 illegal cannabis production sites in
British Columbia (figures from the Drug Enforcement Administration), while RCMP
narcotics specialists, the next day, put the figure at 7,000. Regardless of the
true number, the figures, as may be seen, must necessarily be considered very
carefully.
As to
growing methods, soil‑based production is still the most popular, but the
more sophisticated, hydroponic and aeroponic,[22]
methods are expanding, particularly among criminal gangs that have the necessary
infrastructure.
It
is not uncommon to find indoor grow operations involving over 3,000 plants.
Those figures vary considerably from one province to another, overall less than
10 percent of all marihuana seized in Canada was grown using hydroponics (a
method of growing plants with the roots in nutrient mineral solutions rather
than in soil). Indoor grow operations still rely mostly on soil‑based
organic cultivation but hydroponics is gaining in popularity. Despite the
availability of highly sophisticated technologies designed to increase the yield
even more, most growers do not bother to go to such lengths, preferring simpler
and proven methods. Marihuana remains the most popular illicit drug, both in
terms of consumption and trafficking. The annual marihuana production has been
estimated to be around five million plants. Given the relatively low cost
of setting up a grow operation and the considerable profits it generates, this
activity has become increasingly attractive, even to otherwise law‑abiding
citizens. In the majority of regions, large operations are invariably run by
outlaw motorcycle gangs, although Asian‑based organizations have been
making inroads in British Columbia and Alberta. More and more groups are using
"crop sitters" and other go‑betweens to tend their plantations.
This hands‑off approach makes it difficult for police to link the
operation to the people who are actually behind it. Outdoor crops are often
grown on Crown lands located in remote areas in order to reduce the risk of
detection. [23]
In all,
with considerable reservations as to the validity of the data, the Committee
submits the following:
|
|
Marijuana |
Hashish |
|
Estimated
quantity ‑ national production |
800 tonnes approximately
50% |
100 tonnes ? |
|
Source |
National production (British Columbia, Ontario, Quebec) Imports: Mexico, Jamaica |
Imports: Pakistan, Afghanistan, Morocco |
|
Value (wholesale) |
$2,000 to
$4,000/pound |
? |
|
Retail value (ounce) |
$225 to $250 |
$325 to $350 |
Properties of cannabis
Classified
in the pharmacopoeia as a hallucinogenic, psychodysleptic or psychotomimetic,
cannabis is a disrupter or modulator, that is to say that it alters perceptions
and emotions. Classified in the international conventions and national
legislation as a narcotic, cannabis belongs to the class of psychotropics which
comprises five major groups: depressants (alcohol, Valium), stimulants, minor
(coffee, nicotine) and major (cocaine, amphetamines), disrupters (cannabis,
LSD), antipsychotics and medication for mood disorders (lithium).
More
than 460 known chemical constituents are present in cannabis.[24]
Of that number, more than 60 are identified as cannabinoids. The main active
ingredient in cannabis, which was identified by the team of Dr. Mechoulam
in 1964,[25]
is D9‑tetrahydrocannabinol,
common called THC. Other cannabinoids present in Indian hemp include
delta‑8‑tetrahydrocannabinol, cannabinol and cannabidiol, but they
are present in small quantities and have no significant effect on behaviour,
compared to D9‑THC,[26]
although they can modulate the product's overall effect.[27]
Cannabinol also has anti‑inflammatory effects.
For a
better understanding of the effects of cannabis discussed in the following
chapters, we will first consider its pharmacological properties. Consequently,
readers may skip this technical section without risk of not properly
understanding the rest of the report. In the following paragraphs, we first
discuss D9THC
levels and, second, specifically examine the pharmacological properties of that
substance.
D9THC Concentrations
The D9THC
content of marijuana generally varies in natural growing conditions from 0.5 to
4%.[28]
D9THC
content serves first as a basis for distinguishing the drug type of plant from
the fibre type: permitted concentrations vary by country - in Canada, as in
France, it is 0.3% for the fibre type. For more than a decade now, techniques
for selecting powerful strains and cultivation (in greenhouses and
hydroponically) have made it possible to achieve D9THC
concentrations of 15% or more. D9THC
content is also used to distinguish between various cannabis products and thus
to determine their price: the content of sinsemilla, for example, generally
varies between 7% and 14% and is more expensive than "regular"
cannabis.
The
question of D9THC
content, its variability, how it is determined and its effects has raised
numerous issues. While all specialists agree that maximum active ingredient
concentrations have increased over the past 20 years, opinion is divided on
average concentrations in cannabis available on the market. Estimates vary as to
the preponderance and consequences of D9THC
concentrations.
First,
it should be emphasized that studies show that concentrations are subject to
extreme variability, for a number of reasons. First, failing a control system at
source, the D9THC
content of marijuana is estimated on the basis of police seizures. However, only
a portion of the drug seized is analyzed for THC content,[29]
and analyses are not all equally reliable, depending on how police or customs
officials conducted the seizures and how the products were preserved and
transported to the lab. In addition, between a seized product in clandestine lab
or at a customs post and the product sold on the street, a number of changes can
be made: tobacco, herbs and other products can be added to the gram of
"pot" sold at a school which alter the nature of the drug and thus the
quantity of active ingredient. This is even truer for hashish, as seen above in
the example on processing in Morocco.
Second,
since cannabis is a widespread illegal product, it is impossible to take a
representative sample of the drug available on the market at a given time for
analysis. Thus it is impossible to measure the difference between the D9THC
content of cannabis seized at the production or delivery site and that of
cannabis used by individuals. And third, the active ingredient concentration
varies with the geographical area of origin, climatic conditions and production
conditions. Likely circulating in the market at any given time is a significant
variety of cannabis products reflecting the diverse conditions in which they
were produced. It follows that two samples seized in Vancouver in the same week
could have very different concentrations, as would be the case for samples
seized the same week in Vancouver, Montreal and St. John's.
Experts
told the Committee that cannabis in the Canadian market was 700% more powerful
than the same drug in the 1970s. Some suggested that the average D9THC
content of cannabis on the market is approximately 30%, compared to 3% to 4% in
the 1970s.
The
cannabis used today is up to 500 percent higher in THC - that is a range
between five percent to 31 percent - than the cannabis most adults
remember from the 1960s and 1970s. [30]
In its
1999 annual report, the Royal Canadian Mounted Police estimated the average
content of seizures at 6%.[31]
In Quebec, the Montreal Police Department asserted that the THC content of
cannabis is now 25%. In a private meeting with Committee members, RCMP narcotics
experts in British Columbia emphasized that it is impossible
in the current state of affairs to determine the average content of cannabis in
the country or in a given province, in particular as a result of the extreme
variability of seizures and methods of analysis. The officers who conduct the
seizures do not always pay attention to the manner in which they preserve the
product, such that it may lose its D9THC
content: heat, light and humidity affect the stability of cannabis. Lastly, the
experts providing cannabis for therapeutic purposes whom we met said they kept
various grades of cannabis, based in particular on D9THC
concentrations, and that, in certain cases, the products offered to patients
reached concentrations of 27%.
The most
exhaustive studies on changes in D9THC
levels in cannabis have been conducted in Australia, the Netherlands, France and
the United States. They show, first, that more powerful products have appeared
in the market beside the traditional forms of cannabis: "skunk" (a
variety originating in the United States and the Netherlands),
"super‑skunk" and "pollen" (stamens of male plants).
Canada has not lagged behind, with BC Bud
and Quebec Gold in particular.
More
specifically, the studies on D9THC
concentrations show similar trends:
·
In Australia, a
study by Wayne and Wendy on 31,000 seizures conducted between 1980 and 1997
shows that average content varied little over the period and was between 0,6 %
and 13 %. Among other things, it appears that the main development has been a
more significant selection than previously of the parts of the plant with the
highest concentrations.[32]
The authors of this study make the following observation which applies equally
to Canada:
A
number of factors probably explain the persistence of the belief that the THC
content of cannabis plants in Australia has increased 30 fold in the absence of
any supporting data. First, defenders of the claim often point to reports of
single samples with unusually high THC content tested by the police. At best,
such samples indicate the maximum THC content that has been achieved (assuming
that there were no errors in the test results) but they do not tell us what the
THC content is in the cannabis that is typically used by consumers. Second,
biases in the sampling of tested cannabis are amplified by the attention that
the print and electronic media give to unusually potent samples, creating the
false impression that cannabis with exceptionally high THC is the norm. Third,
uncontested repetition of these assertions in the media has established them as
“fats”; those who context these claims are asked to prove that they are
false rather than the (usually nameless) proponents being asked to provide
evidence that they are true. Fourth, an increase in average THC content seems to
explain an apparent increase in the number of cannabis users who experience
problems as a consequence of their use. [33]
·
In the
Netherlands, the Drug Information
Monitoring System of the Trimbos Institute has conducted various studies
since 2000 on average D9THC
content. The local variety, Nether‑Weed,
contained an average of 8.6% THC in 2000 and 11.3% in 2001, whereas
imported varieties were stable at approximately 5%. One of the reasons given for
this difference was that the local variety was fresher and contained a lower
ratio of cannabinol to D9THC. In
addition, Nether‑Weed resembles
sinsemilla, which comes from the unfertilized flowers of the female plant and is
cultivated in greenhouses.
·
In France, the
Roques report referred to concentrations of up to 20% in the case of certain
Dutch hydroponic varieties.[34]
In its recent report, France's Institut
national de la santé et de la recherche médicale notes a toxicological
study conducted by Mura on the D9THC
concentrations of seizures since 1993. From 1993 to 1995, the average
concentration was 5.5%, but approximately 8% since 1996, with spikes of up to
22%.[35]
In 2000, 3% of marijuana samples analyzed contained D9THC
levels of more than 15%.
·
Lastly, in the
United States, data for 2000 show an average concentration of 6%, compared to
4.1% in 1997. In fact, recalling a study recently conducted in Mississippi, Dr. John Morgan
noted:
(…)
in the midst of this furore over the remarkable increases in marijuana potency,
it is interesting that the potency of the commercial crop sold in the United
States has not varied enormously over the 30 years that potency has been
assessed by the analysis of THC content in criminally seized marijuana. In fact,
I recently looked at the report, which also comes from Mississippi, that the
mean THC content of some 40,000 seizures since 1974 is about three percent.
It has gone up in the last 10 years. In fact, in the last 10 years I
believe the arithmetic mean is more than four percent while in the 10 years
before that it was about 3.5 percent. [36]
The
following table summarizes some of the data on a historical basis for certain
countries.
Year
analysed
|
Domestic Marijuana (USA) Foreign Marijuana (Netherlands) |
Sinsemilla (USA) Nether-Weed (Netherlands) |
|
|
≥ 3 %
≥ 5 %
≥ 9 % |
≥ 3 %
≥ 5 %
≥ 9 % |
|
USA, 19961 |
63%
25%
3% |
93%
77%
49% |
|
USA, 19971 |
63%
29%
6% |
96%
85%
64% |
|
USA, 20002 |
Average of 6.07%
(DEA) |
Average of 13,65%
(DEA) |
|
Netherlands, 2000-20011 |
75%
48%
7% |
93%
87%
35% |
|
Netherlands, 2001-20021 |
80%
55%
4% |
100%
99%
78% |
|
Australia, 19973 |
Between 0.6% and 13% |
|
|
Western Australia |
Average of 3,8% |
|
|
Canada 19994 |
Average of 6% |
Not available |
(1)
Source: Rigter H. and M. von Laar (2002) " Epidemiological
Aspects of Cannabis Use", International Scientific Conference on Cannabis,
Brussels, page 32.
(2)
Drug Enforcement Administration,
http://www.usdoj.gov/dea/concern/marijuana.html
(3)
Source: Hall, W. and W. Swift (2000) op.
cit., page 505
(4)
Source: RCMP, Annual Report for 1999.
In
short, it appears that the main change has been in maximum concentrations
obtained as a result of sophisticated cross‑breeding and cultivation
methods, whereas average concentrations have not significantly changed over the
past 30 years.[37] What conclusion can be
drawn from this? In the minds of some, if cannabis could still be called a
"soft drug" in the 1970s, that is no longer the case today. Some are
not reluctant to say it is a drug comparable to heroin or cocaine in its
addictive power. As an example, the Canadian Police Association has issued the
following opinion on the risks associated with cannabis.
Generally,
marijuana and its derivative products are described [as soft drugs] to distance
the drug from the recognized harm associated with other illegal drugs. This has
been a successful yet dangerous approach and contributes to the misinformation,
misunderstanding and increasing tolerance associated with marijuana use.
Marijuana is a powerful drug with a variety of effects. (…) Marijuana use is
associated with poor work and school performance and learning problems for
younger users. Marijuana is internationally recognized as a gateway drug for
other drug use. Risk factors for marijuana dependence are similar to those of
other forms of drug abuse. [38]
Others
associated the increase in demand for treatment for cannabis dependence with the
increase in active ingredient concentrations. As the National Post reported:
The
potent BC Bud, which has a THC content as high as 25% compared to the 2% typical
in the 1970s, is also leading to health concerns in the United States.
Admissions for marijuana drug treatment in Washington State now exceed the rate
for treatment of alcoholism. Cannabis admissions in Cook County, Ill., have
risen by 400% in the last year. [39]
Can it
be said that cannabis has in fact become a "hard" drug like cocaine
and heroin? Apart from the validity of the effects of cannabis itself as
described by the Police Association, and as will be discussed in detail in the
Chapter 7, that contention does not take into account the way in which the
drug is used or the lack of knowledge of the effects of D9THC
concentrations. Studies on the ways in which cannabis is used, considered in
Chapter 6, show that regular users appear to prefer medium to mild
cannabis, and that they adjust their use to the strength of the drug. Interviews
with individuals who use cannabis for medical purposes tend moreover to confirm
this perception. More significantly, for lack of any specific studies on the
question, the effects of higher D9THC
concentrations are simply not known. Lastly, as will be shown in the following
section, the bio‑availability of D9THC,
that is to say the proportion that is actually absorbed by the body following
combustion, is highly variable. As emphasized in the report of the World Health
Organization (WHO) on cannabis, considering all these factors, the actual
quantity of THC absorbed by the cannabis user is difficult to estimate.[40]
Ultimately, while it can be a legitimate preoccupation, the real issue of D9THC
content has more to do with our ability to control it and better know its
effects, rather than making all kinds of alarmist and unfounded statements about
its level.
Pharmacokinetics [41]
Upon
inhalation, and depending on the smoker's way of smoking and smoking experience,
between 15% and 50% of the D9THC
present in the smoke is absorbed into the bloodstream. The percentage also
depends on the D9THC
concentration in the smoked product. The substance is absorbed very quickly, and
maximum blood concentrations are achieved in less than 15 minutes after the
start of inhalation. The effects felt almost immediately after absorbing the
smoke diminish gradually over the next 60 minutes and generally last a
maximum of three hours after inhalation. In other words, THC levels in the
blood plasma are highest immediately after absorption, whereas maximum effects
are felt approximately 30 to 40 minutes later. The following table
reproduced from the ISERM collective assessment, shows the time to appearance
and duration of detection of cannabinoids in the blood.[42]
Concentration, time to
appearance1 and duration of detection2 of cannabinoids in
the blood after smoking a marijuana cigarette containing 15.8 mg or 33.8 mg
of D9THC
|
Component |
Maximum
concentration |
Time to appearance of peak (hr) |
Duration of detection (hr) |
|
D9THC |
84.3 (50‑129)3 162.2 (76‑267)4 |
0.14 (0.10‑0.17) 0.14 (0.08‑0.17) |
7.3 (3‑12) 12.5 (6‑27) |
|
11‑OH‑D9THC |
6.7 (3.3‑10.4) 7.5 (3.8‑16.0) |
0.25 (0.15‑0.38) 0.20 (0.15‑0.25) |
4.5 (0.54‑12) 11.2 (2.2‑27) |
|
D9THC‑COOH |
24.5 (15‑54) 54.0 (22‑101) |
2.43 (0.8‑4.0) 1.35 (0.54‑2.21) |
84.0 (48‑168) 152.0 (72‑168) |
(1)
average interval between start of consumption and appearance of a
concentration peak
(2)
average interval between start of consumption and moment when lowest
concentration of component is detected (> 0.5 mg/ml)
(3)
cigarette containing 13.8 mg (1.75%) of D9THC
(4)
cigarette containing 33.8 mg (3.55%) of D9THC
Bio‑availability
of D9THC
is slower and weaker when the drug is ingested orally (cookies, cakes, herbal
teas): approximately 4% to 12%; although slower to be felt and different in
quality, its effects are longer lasting.
In all,
we do not know how the effects of THC (concentration) interact with personal
factors (way of smoking, health status, alcoholism or medication). However, it
is likely that the same THC concentration does not have the same effect on all
smokers, which moreover tend to be confirmed by the plasticity of cannabis in
the hormonal stream (see below).
D9THC
is highly lipophilic and is quickly distributed to all fatty tissues, including
the brain. It is also characterized by an entero‑hepatic cycle and renal
reabsorption which results in persistent effects. In a driving simulator study,
a significant linear correlation was found up to seven hours following
absorption, particularly on the trajectory control.
D9THC
undergoes oxydative metabolism resulting in the production of various elements,
in particular 11‑hydroxy‑tetrahydrocannabinol (11‑OH D9THC)
a psychoactive metabolite which, transported by albumin, whereas D9THC
attaches mainly to lipoproteins, penetrates the brain more deeply than D9THC; 8 b‑hydroxy‑D9‑tetrahydrocannabinol,
potentially psychoactive but whose action would be negligible; and various other
components not known for their psychoactive effects. In addition to the
potentially psychoactive elements, cannabis contains approximately 200 derivatives
of combustion and pyrolysis comparable to those found in tobacco, though some of
which are highly carcinogenic and are more concentrated in cannabis smoke than
tobacco smoke.
Cannabinoids
are eliminated in various ways: through digestion, the kidneys and perspiration.
Approximately 15% to 30% of D9THC in
the blood is eliminated in urine, 30% to 65% through stools. Because it binds
strongly to tissues, D9THC is
eliminated slowly in urine: the urine of regular heavy users contains traces of D9THC‑COOH
27 days after they have last used cannabis.
Regular
users metabolize D9THC
up to twice as fast as individuals who have never previously used the drug. One
study showed, in particular, that the intravenous administration of one 5 mg
dose of D9THC
resulted in higher blood levels in regular users than occasional users.[43]
Cannabinoids
act on the body through the endogenous cannabinoid system, consisting of
neurochemical substances (endogenous ligands) and specific receptors. The
behavioural and central effects of cannabis are due to the agonistic action of
its main ingredients (in particular D9THC,
exogenous cannabinoid), on the endogenous cannabinoid receptors (anandamide,
2‑arachidonoylglycerol) present in the nervous tissues of the brain.
Although
the chemical structure of D9THC was
identified by Mechoulam in 1964,[44]
it wasn't until very recently that the characteristics and location of the
endogenous cannabinoid system was determined.[45] Two types of cannabinoid
receptors have been isolated: CB1 in 1990[46]
and CB2 in 1993.[47] CB1 is mainly expressed
in the central and peripheral nervous system. CB2 is expressed essentially in
the cells of the immune system. It follows from this distribution that CB1 is
essentially involved in psychotropic effects and CB2 in immunomodulatory
effects.
The main
endocannabinoids are arachidonoylethanolamide (also called anandamide - a word
derived from Sanskrit, literally meaning congratulated) and
2‑arachidonoylglycerol (2‑AG). These are the only two endogenous
molecules known to be capable of binding to cannabinoids receptors CB1 and CB2
and replicating the pharmacological and behavioural effects of D9THC.
Anandamide levels in the brain are comparable to those of other
neurotransmitters such as dopamine and serotonine. The highest levels
corresponding to high CB1 density areas, that is to say the hippocampus,
striatum, the cerebellum and the cortex. Like anandamide, 2‑AG reproduces
all the behavioural effects of D9THC or
anandamide, but its action is less powerful.
The CB1
receptors are among the most abundant neuronal receptors in the central nervous
system, and their distribution correlates remarkably with the behavioural
effects of cannabinoids on memory, sensory perception and control of movements,
as shown in the table below.
Location of CB1 receptors in
the CNS and correlated pharmacological effects [48]
|
Structures |
Marking |
Physiological
consequences |
References |
|
Forebrain Amygdala Olfactory systems Cerebral cortex Basal nuclei Hippocampus Thalamus/hypothalamus Midbrain Grey nucleus Colliculi Optic nuclei Black substances/ventral tegmental area Hindbrain Grey periaqueductal area Locus ceruelleus Raphe Bridged nucleus Brainstem Cerebellum |
+ + ++ ++ ++ + ‑ ‑ ‑ ‑ + ‑ ‑ ‑ ‑ ++ |
Cognitive effects Locomotive effects Cognitive effects (short-term memory inhibition) and antiepileptic
action Endocrine and antinociceptive effects Antinociceptive effects No lethal dose, no acute mortality Motor effects (balance) |
Herkenham et al., 1990 Herkenham, 1992 Tsou et al., 1998, 1999 Katona et al., 1999 Rinaldi‑Carmona et al., 1996 Matsuda et al., 1990, 1993 Hohmann, 1999 Marsiaco and Lutz, 1999 Westlake et al., 1994 |
++: abundant marking; +: intermediate marking;
‑: little or no marking.
This
concentration of CB1 receptors largely explains the effects of D9THC.
Intense expression of CB1 receptors in the basal nucleus and molecular layer of
the cerebellum is thus consistent with the inhibiting effects of cannabinoids on
psychomotor performance and motor coordination. Their expression in the cortex
and hippocampus is consistent with the modulation of elementary forms of
learning, explaining in particular the reversible deleterious effects on
short-term memory and cognitive function. Their lack of marking in the brainstem
explains the absence of acute toxicity or lethal doses of cannabis derivatives.
The CB1 receptors in the thalamocortical system participate in the sensory
disturbances and analgesic properties of cannabis. Similarly, the presence of
receptors in the periaqueductal area and the dorsal horn of the spinal cord
contribute to its antinociceptive power.
We also
note that the CB1 receptors do not merely inhibit brain function. As a result of
circuit effects, cannabinoids can stimulate certain neuron populations, in
particular dopaminergic cells in the mesolimbic pathway. Together with the
observation that prolonged treatment with cannabis (at doses corresponding to
the equivalent of 575 cannabis cigarettes a day!) appears to induce lasting
adaptive changes to the central nervous system and to the positive relationship
between cannabinoids and stress hormones (corticotrophine), this explains the
difficulties (irritability, sleep disorders and so on) observed in regular users
when they have stopped using cannabis. We return to this issue in the Chapter 7
in the discussion on cannabis tolerance and dependence.
Lastly,
recent works suggest there are significant interindividual variations in the
effects of cannabinoids depending on sex steroid hormones in men and women: it
appears that the effects of exogenous and endogenous cannabinoids can be
modulated by the hormonal state of each individual and that, in exchange, the
CB1 receptors and endocannabinoids are able to regulate hormonal activity.
As was
observed in the WHO report in 1997, various research questions remain
unanswered, in particular how and to what extent cannabis use alters the
endogenous cannabinoid and what the relationship is between blood plasma
cannabinoid levels and induced behavioural effects.
Conclusions
In
conclusion, the Committee makes the following findings:
Conclusions
of Chapter 5
|
|
|
On production On THC |
Ø The size of the cannabis market is estimated at 800 tonnes a year. Ø The size of the national production has significantly increased, and it is estimated that 50% of cannabis available is now produced in the country. Ø The main producer provinces are British Columbia, Ontario and Quebec. Ø Estimates of the monetary value of the cannabis market are unreliable. For example, if 400 tons are grown yearly in Canada, at a street value of $225 per ounce, the total value of the Canadian production would be less than $6 billion per year, less than the often quoted value of the BC market alone. Ø An unknown proportion of national production is exported to the United States. Ø A portion of production is controlled by organized crime elements. Ø THC is the main active ingredient of cannabis; in its natural state, cannabis contains between 0.5% and 3% THC. Ø Sophisticated growing methods and genetic progress have made it possible to increase THC content in recent years, but it is impossible to estimate the average content of cannabis available in the market; it is reasonable to consider that content varies between 6% and 31%. Ø THC is fat soluble and readily spreads in the innervated tissues of the brain; it reaches a peak in the blood plasma in less than nine minutes and falls to approximately 5% after one hour. Ø The body is slow to eliminate THC and inactive THC metabolites can be detected in urine up to 27 days after use in the case of regular users. Ø Psychoactive effects generally last two to three hours and as many as five to seven hours after use. |
[1]
See in particular INSERM (2001) Cannabis.
Quels
effets sur le comportement et la santé ?
Paris: Les Éditions
Inserm, page 143 passim; Ben Amar (in preparation); Wheelock, B.B.
(2002) Physiological and Psychological
Effects of Cannabis: Review of the Findings. Report prepared for the
Senate Special Committee on Illegal Drugs, Ottawa: Senate of Canada.
[2]
This section draws freely on various papers, in particular those by
Ben Amar (in preparation), of INSERM, op.
cit., and Pelc, I., (2002) (ed.) International
Scientific Conference on Cannabis, Brussels. In particular, we wish to
thank Professor Ben Amar for his permission to reproduce the
plates.
[3]
On these questions, see in particular: McKim W.A. (2000)
"Cannabis" in McKim, W.A. (ed.) Drugs and Behaviour. An Introduction to Behavioral Pharmacology. Upper
Saddle River: Prentice Hall; Health Canada (1990) Straight Facts About Drugs and Drug Abuse. Ottawa:
Department of Supply and Services; and Comité permanent de lutte à la
toxicomanie (2001) Drogues. Savoir plus. Risquer Moins. (Édition québécoise) Montréal:
Stanké.
[4]
United Nations Office for Drug Control and Crime Prevention (2001) World
Drug Report 2001. Oxford: Oxford University Press, pages 30‑32.
Available on line at http://www.undcp.org/adhoc/world_drug_report_2000/report_2001‑01‑22_1.pdf.
[5]
Labrousse, A.
(2000) Drogues. Un marché de dupes. Paris:
éditions alternatives; see also "L’approvisionnement des marchés
des drogues dans l’espace Schengen." Les
Cahiers de la Sécurité Intérieure, 32, 2e trimestre
1998.
[6]
See, for example, in OGD (1996) Atlas
mondial des drogues. Paris: PUF.
[7]
Royal Canadian Mounted Police (2002) Drug
Situation in Canada (2001). Ottawa: author.
[8]
Royal Canadian Mounted Police (2000) Drug
Situation in Canada (1999). Ottawa: author.
[9]
UNDCP (2000) op. cit.
[10]
The Committee invited the Executive Director of UNDCP or a delegate
to testify before it, but the invitation was turned down.
[11]
"Stumbling in the Dark", The
Economist, July 28 - August 3, 2001.
[12]
Royal Canadian Mounted Police (2000), op.cit.
[13]
World Geopolitics of Drugs (1999) Annual
Report 1998/1999. Paris:
WGD, page 178.
[14]
Greater Toronto Area Combined Forces Special Unit (2002) Fact
Sheet - Heroin. Available on line at: http://www.cfseu.org/heroin.html.
[15]
Mr. Paul Kennedy, Testimony before the Senate Special
Committee on Illegal Drugs, June 10, 2002.
[16]
Ibid.
[17]
Royal Canadian Mounted Police (2000) op.
cit..
[18]
National Post, May 17, 2002. The Committee is interested, and
somewhat amused, to note that this article and a previous report on the
Global television network on May 13, 2002, outlining the concerns of
American representatives, followed the Committee's publication of its
Discussion Paper.
[19]
International Narcotics Control Board (2001) Report of the International Narcotics Control Board for 2000.
Available on line at: http://www.incb.org.
[20]
Royal Canadian Mounted Police (2000) op.
cit..
[21]
RCMP, private meeting.
[22]
Technique whereby the roots are suspended and sprayed regularly with
water enriched with nutrient material, still very rare and the effectiveness
of which remains to be proven. (Source: RCMP (2002)).
[23]
RCMP, Drug Situation in Canada (1999) op. cit..
[24]
See in particular Grinspoon, L. and J.B. Bakalar (1997) Marijuana.
The Forbidden Medicine. New Haven and London: Yale University Press;
Clark P.A. (2000) "The ethics of medical marijuana: government
restrictions vs. medical necessity", Journal
of Public Health Policy, 21: 40‑60; as well as Wheelock (2002) for
the Senate Committee.
[25]
Gaoni, Y. and R. Mechoulam (1964) "Isolation,
structure and partial synthesis of an active constituent of hashish", Journal
of the American Chemistry Society, 86: 1646‑1647; and Mechoulam, R.
and Y. Gaoni (1965) "A total synthesis of
delta‑9‑tetrahydrocannabinol, the active constituent of
hashish", Journal of the American
Chemistry Society, 87: 3273‑3275.
[26]
Smith, D.E. (1998) "Review of the American Medical
Association Council on Scientific Affairs Report on Medical Marijuana",
Journal of Psychoactive Drugs. 30:
127‑136; McKim W.A. (2000) "Cannabis", in McKim, W.A.
(ed.) Drugs and Behavior. An
introduction to behavioral pharmacology. Upper Saddle River: Prentice
Hall.
[27]
Ashton, C.H. (2001) "Pharmacology and effects of cannabis:
a brief review", British Journal
of Psychiatry. 178:
101‑106.
[28]
Huestis, M.A et al. (1992)
"Characterization of the absorption phase of marijuana smoking", Clinical Pharmacology and Therapeutics, 52: 31‑41.
[29]
Note, for example, that, in the United States, there is no systematic
method for measuring THC. As emphasized in a comparative analysis of changes
in price of heroin, cocaine and marijuana, "Another problem is that the
DEA does not test marijuana for THC content, so there is no marijuana
counterpart to the pure grams reported for cocaine and heroin. The
difficulty this causes is the STRIDE data provide no basis for adjusting
price changes for marijuana’s quality." Abt Associates (2001) The
Price of Illicit Drugs: 1981 through the Second Quarter of 2000. Washington,
DC. Report prepared for the Office on National Drug Control Policy.
[30]
Testimony of Mchael J. Boyd, Chair of the Drug Abuse
Committee and Deputy Chief of the Toronto Police Service, for the Canadian
Association of Chiefs of Police, Senate Special Committee on Illegal Drugs,
Issue No. 14, page 74.
[31]
Royal Canadian Mounted Police (1999), Annual Report.
[32]
Wayne, H. and S. Wendy (2000) "The THC content of
cannabis in Australia: evidence and implications", Australian and New Zealand Journal of Public Health. 24:
503‑508.
[33]
Ibid., page 504.
[34]
Roques, B. (1999) La
dangerosité des drogues. Paris: Odile Jacob.
[35]
INSERM (2001) Cannabis: quels
effets sur le comportement et la santé? Paris: Les Éditions Inserm.
[36]
Dr. John Morgan, Professor at the City University of New
York Medical School, testimony before the Senate Special Committee on
Illegal Drugs, June 11, 2001, Issue No. 4, page 29.
[37]
ElSohly, M.A., et al.
(2000) "Potency trends of delta9‑THC and other cannabinoids in
confiscated marijuana from 1980‑1997", Journal
of Forensic Sciences, 45(1): 24‑30.
[38]
Sergeant Dale Orban, Regina Police, at the Senate Committee
hearing on May 28, 2001.
[39]
National Post, May 17, 2002.
[40]
World Health Organization (1997) Cannabis:
a health perspective and research agenda. Geneva: WHO, 1997. On line at:
www.who.org.
[41]
This section is based to a large extent on the INSERM 2001 report as
well as the European scientific report 2002 and the survey work done by
Wheelock 2002 for the Committee.
[42]
INSERM (2001) Cannabis. Quels
effets sur le comportement et la santé? Paris:
author, page 340.
[43]
Cited in INSERM (2001) op. cit.,
page 148.
[44]
Guoli and Mechoulam (1964) op.
cit.
[45]
Devane, W.A. et al.
(1992) "Isolation and structure of a brain constituent that binds to
the cannabinoid receptor", Science,
258 (5090): 1946‑1949.
[46]
Matsuda, L.A. et al. (1990)
"Structure of a cannabinoid receptor and functional expression of the
cloned DNA", Nature,
346(6284) 5561‑564.
[47]
Munro, S. et al. (1993)
"Molecular characterization of a peripheral receptor for
cannabinoids", Nature, 365:
61‑65. Note that a recent scientific conference of the National
Institute on Drug Abuse in the United States reported on the work of
researchers on the hypothesis that there are additional receptors and other
ligands. To our knowledge, the latter have not yet been formally identified
in the research setting.