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DEA Scientific Study Of Several
Cannabis Marijuana Studies Of THC
{1997, above), a one gram cigarette containing 1% THC
containing cannabis, would contain 10 mg of THC -a dose well capable of
producing a social high.
Return
Back To Main Medical Reports Page
Carlini et al. (1974) examined 33 subjects who smoked
marijuana cigarettes with different ratios of constituent cannabinoids. The
plant containing 0.82% THC produced larger than expected results based on the
estimates from the THC content. Smoking a 250 mg cigarette containing 5.0 mg of
?9-THC induced more reactions graded 3 and 4 than 10 or 20 mg of?9-THC . It was
further observed that the psychological effects (subjective "high/1)
started around 10 min after the end of the inhalation, and reached a maximum 20
to 30 min later, subsiding within 1 to 3 hrs. The peak of psychological
disturbances, therefore, did not coincide in time with the peak of pulse rate
effects. Carlini et al., suggested that other constituents of the marijuana were
interacting synergistically with the THC to potentiate the subjective response
induced by the smoking of the cigarette. Karniol and colleagues (1973,1974) have
clearly demonstrated that cannabidiol (CBD)blocks some of the effects induced by
THC, such as increased pulse rates and disturbed time perception. More
importantly, CBD blocked some of the psychological effects of THC, but not by
altering the quantitative or intensity of the psychological reactions. CBD
seemed better able to block the aversive effects of THC. CBD changed the
symptoms reported by the subjects in such away that the anxiety component
produced by THC administration was actually reduced. The animal subjects of one
study showed greater analgesia scores with a CBD+THC combination (1973) and the
human subjects from the other study (1974) showed less anxiety and panic but
reported more pleasurable effects. CBD may be best seen as an
"entourage" compound (Mechoulam, Pride, DiMarzo, 1998) which is
administered along with THC and results in a functional potentiation of THC's
behavioral and subjective effects. This potentiation can be in both the
intensity and/or duration of the high induced by marijuana. According to Paris
& Nahas (1984) the CBD:THC ratio in industrial or fiber type hemp is 2:1.
Relevant to the current petition, the CBD:THC ratio producing the greatest
increase in euphoria in the Karniol et al. studies was 2:1 (60:30 mg) .
Jones & Pertwee(1972) were first to report that the
presence of cannabidiol inhibited the metabolism of THC and its active
metabolite. These data were soon replicated by Nilsson et al., (1973) .Bronheim
et al., (1995) examined the effects of CBD on the pharmacokinetic profile of THC
content in both blood and
12
brains of mice. CBD pretreatments produced a modest
elevation in THC-blood levels; area under the kinetics curve of THC was
increased by 50% as a function of decreased clearance. CBD pretreatments also
modestly increased the Cmax, AUC, and half-life of the major THC metabolites in
the blood. The THC kinetics function showed a 7 to 15-fold increase in the area
under the curve, a 2 to 4-fold increase in the half-life, as well as the tmax.
CBD pretreatments resulted in large increases in area under the curves and
half-lives of all the THC metabolites in the mice brains. The inhibition of the
metabolism of THC and its psychoactive metabolites by CBD may underlie the
potentiation in the subjective effects of THC by CBD in humans.
In addition to THC, hemp material contains a variety of
other substances (e.g., Hollister, 1974), including other cannabinoids such as
cannabidiol (CBD) and cannabinol (CBN) .One comprehensive review described the
activities of 300 capnabinoid compound in preclinical models (Razdan, 1986)
.Since CBD is always present in preparations of cannabis, it may represent a
high CBD:THC ratio in the case of low THC cannabis. Therefore, it is important
to understand the interactions of cannabidiol and ?9-THC.
Structure-activity studies of cannabinoid compounds
characterized cannabidiol in relationship to ?9-THC and other cannabinoids
(Martin et al., 1981; Little et al., 1988). These and other studies have found
that cannabidiol was inactive and did not produce neuropharmacological effects
or discriminative stimulus, subjective effects and behavioral effects predictive
of psychoactive subjective effects (Howlett, 1987; Howlett et al., 1992; c.f.,
Hiltunen and Jarbe,. 1986; Perez-Reyes et al., 1973; Zuardi et al., 1982;
Karniol et al., 1974).
Other studies have reported that cannabidiol has
cannabinoid properties, including anticonvulsant effects in animal and human
models (Consroe et al., 1981; Carlini & Cunha, 1981; Doyle and Spence, 1995)
, hypnotic effects (Monti, 1977) , anxiolytic effects (Musty, 1984; Onaivi, Geen,&
Martin, 1990; Guimarares et al., 1990; 1994) and rate-decreasing effects on
operant behavior (Hiltunen et al., 1988) .
Experiments with cannabidiol in combination with THC have
found that certain behavioral responses induced by THC (i.e., operant,
schedule-controlled responding) were attenuated by cannabidiol (Borgen and
Davis, 1974; Brady and Balster, 1980;
13
Consroe et al., 1977; Dalton et al., 1976; Kraniol and
Carlini, 1973; Karniol et al., 1974; Welburn et 1976; Zuardi and Karniol, 1983;
Zuardi et al., 1981, 1982; Hiltunen et al., ~988) .However, other affects
produced by THC are augmented or prolonged by the combined administration of CBD
and THC or marijuana extract (Chesher and Jackson, 1974; Hine et al., 1975a,b;
Fernandes et al., 1974; Karniol and Carlini, 1973; Musty and Sands, 1978; Zuardi
and Karniol, 1983; Zuardi et al., 1984) .Still other studies did not report any
behavioral interaction between the CBD and THC (Bird et al., 1980; Browne and
Weissman, 1981; Hollister and Gillespie, 1975; JArbe and Henricksson, 1974;
Jarbe et al., 1977; Mechoulam et al., 1970; Sanders et al., 1979; Ten Ham and
DeLong, 1975).
A study to characterize the interaction between CBD and
THC was conducted using preclinical drug discrimination procedures. Rats and
pigeons trained to discriminate the presence or absence of THC, and tested with
CBD administered alone and in combinations with THC (Hiltunen and JArbe, 1986) .
Specifically, in rats trained to discriminate 3.0 mg/kg,
i.p. THC, CBD (30.0 mg/kg) was administered alone and in combination with THC
(0.3 and 1.0 mg/kg, i.p.) .In pigeons trained to discriminate 0.56 mg/kg, i.m.
THC, CBD (17.5 mg/kg) was administered alone and in combination with THC (0.1,
0.3, and 0.56 mg/kg, i.m.) .CBD prolonged the discriminative stimulus effects of
THC in rats, but did not change the time-effect curve for THC in pigeons. In
pigeons, the administration of CBD did not produce any differential effect under
a fixed ratio schedule of reinforcement (Hiltunen and JArbe, 1986) .
These data suggest that CBD may somehow augment or prolong
the actions of THC in rats and had no effect in pigeons. In the present study,
the CBD/THC ratios ranged from 30:1 to 100:1 in rats and enhanced the stimulus
effects of THC. However, similar CBD/THC ratios in pigeons (31:1, 58:1 and
175:1) did not result in any changes to THC's discriminative stimulus or
response rate effects (Hiltunen and Jarbe, 1986) .
It should be noted that cannabidiol can be easily
converted to delta-9 and delta-8-tetrahydrocannabinol. Even industrial hemp
plant material (leaves) , containing high concentrations of CBD, can be treated
in clandestine laboratories to Convert the CBD to delta-9-tetrahydrocannabinol (Mechoulam,
1973) converting a supposedly innocuous weed into a potent smoke product.
14
In conclusion, the "entourage" compound,
cannabidiol, does contribute to all of the effects ascribed to THC, however it
also appears to lack cannabimimetic properties. However, there is no credible
scientific evidence that CBD is a pharmacological antagonist at the cannabinoid
receptor (Howlett, Evans, & Houston, 1992) .There is clear evidence that CBD
can functionally antagonize some of the aversive effects of THC (Dewey, 1986)
.The data from the scientific literature cited above, clearly demonstrate the
ability of CBD to modify some very specific effects of THC. Most importantly,
relative to the euphorigenic effects of THC (which contributes to its abuse
liability), CBD appears to potentiate the psychological or subjective effects of
THC by potentiating the blood and brain THC and 11-0H-THC levels and by
functionally blocking the aversive (anxiety-like) properties of THC.
Abuse Liability Summary:
Preclinical and clinical experimental data demonstrate
that marijuana and ?9-THC have similar abuse liabilities (i.e., drug
discrimination, self-administration, subjective effects) .Both preclinical and
clinical studies show that discontinuation of either marijuana or ?9-THC
administration produces a mild withdrawal syndrome. The effects of THC are
dose-dependent and several studies have found that low-potency THC is
behaviorally active and can produce cannabimimetic-like subjective and
physiological effects.
ACTUAL ABUSE
There are dozens of data collection and reporting systems
that are useful for monitoring the United States' "problem with abuse of
licit and illicit substances. These data collection and reporting systems
provide quantitative data on many factors related to abuse of a particular
substance, including incidence, pattern, consequence and profile of the abuser
of specific substances (cf., Larsen et al., 1995) .
Evidence of actual abuse is defined by episodes/mentions
in the databases indicative of abuse/dependence. Some of the databases that are
utilized by DEA to provide data relevant to actual abuse of a substance include
the Drug Abuse Warning Network (DAWN), National Household Survey on Drug Abuse,
Monitoring the Future survey, FDA's Spontaneous Adverse Events
15
Reports, the American Association of Poison Control
Centers database and reports of the Community Epidemiology Work Group (CEWG).
.
Drug trafficking and diversion data provide strong
evidence that a drug or other substance is being abused. In order to determine
the pattern, incidence, and consequences of abuse and the demographics of
abusers of a particular substance to be controlled, DEA relies on data collected
from a number of sources, including the United States government as well as
state and local law enforcement groups. Information from these sources often
provides a first indication of an emerging pattern of abuse of a particular drug
or substance, and when taken together with other data sources provide strong
evidence that can be used in determining a substance's placement in the
schedules listed in the CSA.
The evidence from epidemiological studies conclude that
marijuana use alone and in combination with other illicit drugs is increasing.
The most recent "Monitoring the Future Study", documented increases in
lifetime, annual and current (within the past 30 days) and daily use of
marijuana by eighth and tenth graders; this increasing trend began in the early
19901s.
Similarly, according the NIDA's "National Household
Survey", marijuana use is increasing with the greatest increase among the
younger age groups (12-17 years of age) .The frequency of marijuana use in the
past year increases significantly among 1217 year olds. This survey also found
that youths who used marijuana at least once in their lives were more likely to
engage in violent or other antisocial behaviors.
Marijuana is the most readily available illicit drug in
the United States. Cannabis is cultivated in remote locations and frequently on
public lands. Major domestic outdoor cannabis cultivation areas are found in
California, Hawaii, Kentucky, New York and Tennessee. Significant quantities of
marijuana were seized from indoor cultivation operations; there were 3,532
seizures in 1996 compared to 3,348 seized in 1995. Mexico is the major source of
foreign marijuana, along with lesser amounts from Colombia and Jamaica (NNICC,
1996) .
Domestically, marijuana is distributed by groups or
individuals, ranging from large sophisticated organizations with
16
controlled cultivation and interstate trafficking, to
small independent traffickers at the local level.
(2)
SCIENTIFIC EVIDENCE OF ITS PHARMACOLOGICAL EFFECTS, IF
KNOWN
Cannabis sativa is unique in that it is the only botanical
source of the terpenophenolic substances referred to as cannabinoids which are
responsible for the psychoactive effects of Cannabis. There are roughly 60
different cannabinoids found in Cannabis (Nahas, 1984; Murphy & Bartke,
1992; Agurell, Dewey & Willette, 1984) but the psychoactive properties of
Cannabis are attributed to one or two of the major cannabinoid substances,
namely delta-9-tetrahydrocannabinol and delta-8tetrahydrocannabinol. In fresh,
carefully dried marijuana, up to 95% of their cannabinoids are present as
(-)-delta-9-(trans)tetrahydrocannabinol carboxylic acid (Nahas, 1984; Murphy
& Bartke, 1992; Agurell, Dewey & Willette, 1984) .The acid form is not
psychoactive, but is readily decarboxylated upon heating to yield
delta-9-tetrahydrocannabinol (neutral form) . Therefore, plant material could be
very high in its "pro-drug" acid form and very low in neutral form but
still be very potent when smoked.
There are two primary factors that influence THC content:
genetic predisposition and environmental influences. Genetic factors are
considered predominant in determining cannabinoid content, although,
fluctuations in weather conditions have greatly enhanced or diminished the THC
content.
Paris & Nahas (1984) have admonished that marijuana is
not a single uniform plant like many of those encountered in nature, but a
rather deceptive weed with several hundred variants. The intoxicating substances
prepared from Cannabis vary considerably in potency according to the varying
mixtures of different parts of the plant, and according to the techniques of
fabrication. According to Paris & Nahas, this basic botanical fact has been
overlooked by physicians and educators, who have written about marijuana as a
simple, single substance, which uniformly yields a low concentration of a single
intoxicant. In addition to changes due to its own genetic plasticity, marijuana
has been modified throughout the ages by environmental factors and human
manipulations, and is not yet a stabilized botanical species (Paris & Nahas,
1984) .
17
According to Paris & Nahas (1984) the terminology used
by Fetterman et al. (1970, 1971) is somewhat misleading, especially with respect
to their contention that environmental factors, including climate, are not as
important as heredity in determining the cannabinoid content of cutigens. The
analyses of Fetterman et al., (1970) were performed according to the technique
by Doorenbos et al., (1971) on plant materials from variants that had been cut
at the stem beneath the lowest leaves and air-dried. Seeds, bracts, flowers,
leaves and small stems
were then stripped from the plant. Most of the small stems
were removed by a 10-mesh screen, and the seeds were eliminated with a
mechanical seed separator. This preparation of marijuana contains less seed and
stem than most of the illicit material available in the United States.
Cannabinoids were then extracted from the plant material and analyzed by
standard techniques.
Other systems of separating Cannabis into drug,
intermediate and non-drug typ~ have been developed. These are typically
determined by chemical analyses based upon the method described by Doorenbos
(1971) which utilizes manicured portions of the Cannabis plant only in
determining percent concentration.
Cannabis sativa has been referred to as a widely
distributed and unstabilized species. Cannabis exhibits extreme polymorphism
(ability to alter, change) in different varieties, dependent upon many factors.
For example, there are at least twenty strains which are cultivated for fiber.
There have been many attempts to classify Cannabis as a function of intoxicant
properties or fiber properties. Such classification efforts are dependent upon
the age of the sample. And there is no totally reliable classification system
based on a single chemical analysis. The plasticity of the genus has prevented
the development of such a system (Turner et al. 1980a,b) .
In a study where twelve strains of Cannabis were grown out
of doors in Southern England (Fairbairn and Liebmann, 1974, Fairbairn et al.,
1971) , the following were determined:
1. Warm climate are not necessary for high THC content.
2. There is considerable THC content variation within and
between plants.
3. Quantitative results of tetrahydrocannabinol
concentration (THC) are highly dependent upon the specific
plant part sampled, the stage of
l8
growth and the size of sample.
4. Certain strains of Cannabis can be THC or cannabidiol (CBD)
rich which does not seem to be dependent upon environmental conditions.
5. However, growing the same strain of Cannabis under
different lighting conditions can produce plants that range from 2.4 to 4.42%THC
concentration (based upon an analysis of the upper leaves) .And finally,
6. THC concentration are dramatically higher on dried
flowering or vegetative tops of the plants relative to middle or lower portions.
In a similar study on the characterization of Cannabis
accessions with regard to cannabinoid content, vis-a-vis other plant characters
(deMeijer, 1992), it was determined that:
1. there exists considerable variation within and among
accessions for cannabinoid content;
2. mean cannabinoid content is strongly affected by year
of cultivation;
3. there is no strict relationship between chemical and
non-chemical traits; and,
4. it is uncommon, but some accessions combine high bark
fiber content and considerable psychoactive
potency.
In 1993 de Meijer reported the results of a government
(Netherlands) funded industrial hemp project designed to investigate the stem
quality, yield, and a comparative analysis to wood fibers. deMeijer found that
the commercial grade industrial hemp seeds, germplasms derived from <0.3% THC
chemovars, demonstrated a significant variation in the average THC content which
ranged from 0.06 to 1.77% in the female dry leaf matter. deMeijer concluded by
stating,
Although high bark fiber content does not necessarily
exclude high THC content, most fiber cultivars have very low THC content and
thus possess no psychoactive
potency
While the data from his own study refutes these
conclusions he does conclude that the industrial hemp plant does not preclude
high THC content.
-
19
A review of these and other studies in the scientific
literature, indicate that THC concentrations vary within portions of the
Cannabis plant (Hanus et al., 1989, 1975) .In some studies, the concentration of
THC can increase as much as 100% from leafy to flowering portions of the same
plant. THC concentrations are known to be elevated on the upper portions of the
plant. In a study published by Fairbairn and Liebmann, (1974) there was
considerable variations between the flowering tops (bracts, flowers, immature
fruits at the ends of shoots) and leafy portions of some specimens. THC content
decreases with age and length of leaves (Paris & Nahas, 1984, p 25) .The
lower, more developed leaves have a low cannabinoid content and the top leaves
have a high cannabinoid content, especially when they are associated with the
bracts of the plant. Cannabinoids are localized in the upper third of the
"stalk" and in the flowers . Therefore, the THC content of specific
portions of a plant, which on a whole plant basis did not exceed 1%, could
significantly exceed this threshold. Very few marijuana users actually
"smoke" the leaves. It is the colas or the flowering portions of the
plants which are utilized and these are exactly the portions of the plant which
would be expected to have the highest concentration of THC.
It is clearly recognized that Cannabis presents a high
degree of genetic plasticity which results in extreme polymorphism in its
different varieties. The hemp first grown in the United States for fiber was of
European origin. The type basic to modern American fiber production, known as
Kentucky, came originally from China. In Europe, there are five to six varieties
with one considered "exceptional" -the Kymington. The plasticity of
the European fiber variety has been clearly shown (Bouquet, 1951; Hamilton,
1912, 1915) .European cultigens planted in dry, warm areas of Egypt to supply
fiber for rope-making were found to produce, within several generations, plants
with high psycho-active ingredients and very little fiber. Cannabis sativa's
botanical and chemical characteristics change markedly as a result of
environmental factors and human manipulation. Doorenbos et al., (1971)
cultivated a Mexican and Turkish variant in Mississippi for three consecutive
generations. During that period, the ?9-THC content did not change in the
Mexican variant but increased in the Turkish variant. In the more controlled
environment of a phytotron (light, humidity, and nutrition controlled) , Braut-Boucher
(1978) , Braut-Boucher & Petiard (1981), Braut-Boucher, Paris, & Cosson
(1977) and Paris et al., (1975) found that the cannabinoid concentrations rose
over a
20
similar three year period. The concentrations rose more
sharply in cool environments (22-12°C: day-night) than in warm environments
(32-12°C) .Some authors have hypothesized that
immediate environmentally caused changes are individual
plant reactions, whereas the progressive changes over generations are linked
with whole populations and constitute a true natural selection. Whether this
evolution is caused by a change of genetic equilibrium (caused by the
environment), or by a modification of the genetic capacity (over time) , is
impossible to say (Paris & Nahas, 1984) .
In 1974 through 1976 the University of Mississippi
cultivated 7 variants of 12 Cannabis plants discovered and collected in 1973
from different areas of Mexico. Cannabinoid content was analyzed weekly during
the cultivation period. Turner, Elsohly, Lewis, Lopez-Santibanez & Carranza
(1982) summarized their findings as follows:
In 1974, vegetative plants of ME-R, ME-K, ME-L, ME-N and
ME-a, at 13 weeks of age had higher ?9-THC content that at weeks 12 and 14. They
showed minimum ?9-THC content at week 15. For the most part, 1974 staminate and
pistillate plants grown in Mississippi produced a low ?9-THC concentration.
In all variants, the average ?9-THC was higher in 1976
than in 1974. Also, a greater fluctuation of ?9-THC was observed in 1976 than in
1974.
These results further establish that Cannabis Sativa L. is
not a stable hybrid plant, but rather, represents characteristics more similar
to an unstable weed.
Marijuana chemistry is complex and cannot be simplified or
extrapolated from anyone or two "active compounds". As early as 1974
this fact was recognized by the United Nations Division on Narcotic Drugs (UN
Doc, 1974) .As highlighted by Turner (1980) , the chemistry of THC is not the
chemistry of marijuana and the pharmacology of marijuana is not the pharmacology
of TRC. Recent findings do suggest that the interactions between cannabinoids is
one of many critical factors in the analysis of the Psychopharmacology of
marijuana.
21
According to Jones (1980) , because of exposure to a wide
range of plant material and the cultural labeling (almost like advertising) of
much of the marijuana experience, marijuana users are particularly subject to
the effects of nonpharmacological variables that alter the subjective response
to marijuana intoxication (Jones 1971, 1980; Cappell & Pliner, 1974; Becker
1967) .As reviewed by Jones (1971) , a number of studies suggest that
experienced marijuana users are more subject to "placebo reactions";
that is, a degree of intoxication disproportionate to the THC content of the
material. This seems particularly true if the individuals are exposed to low
potency marijuana «1.0% THC) . Jones believes that this is a result of
experience and practice at recognizing minimal physiologic cues together with
the smell, taste and other sensations associated with smoking a marijuana
cigarette (Jones 1980, 1971) .Becker 1967 and Cappell & Pliner (1974) have
described a number of psychological factors (expectancy, social setting, etc.)
that appear to synergistically interact to help generate the subjective
experiences engendered by marijuana smoking.
Domino, Rennick, & Pearl (1976) administered THC
injected into tobacco cigarettes to male volunteers. Similar to findings
described by Isbell et al., (1967) they report that 50 ?g of THC into the
cigarettes produced a "social high", while 250 ?g /kg was
"hallucinogenic". Taking 80 kg as the mean weight of their subjects
the authors concluded that a 4.0 mg total THC dose produced a "social
high"; a hallucinogenic dose was 20 mg total THC by inhalation. A standard
19 cigarette of 1% THC fibre-type hemp provides 10 mg of THC. Even allowing for
a 50% loss of THC from sidestream smoke and pyrolysis, smoking this cigarette
provides more than enough THC to produce a "social
high".
In 1968 Neil, Norman, & Nelsen described a set of
studies examining the physiological and psychological aspects of smoked
marijuana. The first batch of Mexican grown marijuana used in the study was
found to contain only 0.3% THC by weight. The potency of this product was
considered to be "low" by the experimenters on the basis of the doses
needed to produce symptoms of intoxication in the chronic users. This low
potency marijuana was able to produce a "high", but only with two 1
gram cigarettes. A second batch was used in later studies. Neil, Norman, &
Nelsen report that marijuana assayed at 0.9% THC (a quantity slightly less than
the 1% THC limit set forth by the petitioners) was rated by the chronic users in
the study to be "good, average" marijuana, neither exceptionally
strong nor exceptionally weak
22
compared to the usual supplies. Users consistently
reported symptoms of intoxication after smoking about 0.5 grams of the 0.9% THC
containing marijuana (half a joint) .With the high dose of marijuana (2.0 grams
of 0.9% THC containing marijuana) all chronic users became "high" by
their own accounts and in the judgment of experimenters who had observed many
persons under the influence of marijuana.
Agurell & Leander (1971) examined the physiological
and psychological effects of low THC-containing cannabis in experienced users.
They reported that 14-.29% of the cannabinoid content of the cigarette was
transferred to the main stream smoke. Based on qualitative and quantitative
analyses, Agurell & Leander demonstrated that as little as 3-5 mg of THC was
needed to be absorbed by the lung in order to produce a "normal biological
high". Further, they found that as little as 1 mg of absorbed THC was
discriminable by all of their chronic user subjects.
In 1982, Barnett, Chiang, Perez-Reyes, & Owens had six
subjects smoke a 1% THC-containing (industrial hemp, as defined by the
petitioner) marijuana cigarette. Significant heart rate and subjective measures
of "high" were measured for 2 hours after each cigarette.
In 1971 Jones reported on the wide variability in THC
concentrations found in street samples:
Specimens gathered in the midwestern United States
contained only 0.1 - 0.5% THC. Thirty specimens selected from seized samples in
the Bureau of Narcotics and Dangerous Drugs Laboratory in San Francisco all
contained less than 1% THC. Samples from the State of California Bureau of
Narcotic enforcement analyzed in our laboratory contained as little as 0.1% THC
and a maximum of 0.9%. ...In a survey done in Ontario, Canada, Marshman and
Gibbons found that of 36 samples alleged to be marijuana with high cannabinoid
content, 34% contained no marijuana at all, and much of the rest was cut with
other plant substances. A generous assumption is that marijuana generally
available in the United States averages about 1.0% THC.
It must be acknowledged that the THC content of
domestically grown and imported marijuana has increased since these reports.
23
However, the description by Weil, Zinberg & Nelson
(1968), Agurell & Leander (1971), Jones (1971) and Barnett et al. (1982)
highlight the historical importance of low THC concentrations contained in
marijuana which provided the basis for the marijuana culture that developed in
the 1970s. The incident described by Jones was not an isolated case of the
inadvertent misrepresentation of the THC content of marijuana extracts. Caldwell
et al., (1969) found that the NIMH-supplied marijuana that they r~ported to have
contained 1.3% THC was analyzed by two independent laboratories and found to
contain as little as 0.2 to 0.5% THC. Similarly, according to Paton &
Pertwee (1973) the THC content of material used by Clark & Nakashima (1968)
, Weil et al., (1968), Weil & Zinberg (1969), and Crancer et al., (1969)
must be expected to be one-third to one-sixth less than stated. This means that
the positive results of all of these studies were the result of a surprisingly
low THC-containing «1.0%) marijuana. The early scientific data on the
subjective effects of marijuana were generated with these samples by experienced
smokers smoking material in this potency range. These experienced marijuana
smokers were reporting that these marijuana samples were of "average
quality"(Mechoulam, 1973) .
In an early study, Jones (1971) utilized 1 gram of plant
material with a THC concentration of 0.9% (9 mg of THC) . Experienced marijuana
smokers were asked to freely smoke marijuana cigarettes for 10 minutes. The
smoking topography of the smokers widely varied and was not controlled in this
set of experiments. Subjects were asked to smoke the entire cigarette.
Subjective state was measured by asking the subjects to make global estimates of
his degree of intoxication on a 0-100 scale. A score of 0 was defined as
"sober" and a score of 100 as the most intoxicated or most
"stoned" they had ever been in any social situation. At the end of the
session (about 3 hrs) , the subject also filled out a 272-item symptom checklist
(SDEQ: subjective drug effects questionnaire) which taps some of the more
unusual emotional, perceptual and cognitive effects produced by psychoactive
drugs. The mean potency rating was 61 for the marijuana containing only 9 mg of
THC. There was a tremendous range in the rating made by individual smokers.
Jones concluded that the smokers may obtain intermittent reinforcement from THC
but where much of the behavior and subsequent response is maintained by
"conditioned reinforcers" such as the whole ritual of lighting up, the
associated stimuli of smell, taste, visual stimuli and so on.
24
Manno, Kiplinger, Haine, Bennett, & Forney (1~70)asked
subjects to smoke an entire 1 gram cigarette containing 1% THC (10 mg; low
potency) .The subjects were told to take 2 to 4 seconds to inhale and to hold
the draw for 30 to 60 seconds. The expired smoke was collected and analyzed for
THC content, as well. During the experiment the subjects smoked the entire
cigarette; in all cases, less than 0.5 mg of THC remained in the residue of each
cigarette. Manno et al. reported that the quantity of THC or other cannabinols
present in a marijuana cigarette was not a reliable indicator of the amount of
cannabinols that were delivered in the smoke of the cigarette. Controlled
smoking experiments through a manufactured smoking machine demonstrated that
approximately 50% of the ?9-THC originally present in the cigarette was
delivered unchanged in the smoke. Manno et al. concluded that a dose of
approximately 5 mg of ?9-THC was delivered which was estimated to be an
administered dose in the range of 50 to 75 ?g per kilogram. These low potency
marijuana cigarettes produced significant motor and mental performance measures
on the pursuit meter test, delayed auditory feedback, verbal output, reverse
reading, reverse counting, progressive counting, simple addition, subtraction,
addition +7, subtract +7, and color differentiation. These low potency
cigarettes also produced significant pulse rate increases and significant
increases on a somatic symptoms checklist. Unsolicited verbal comments from the
subjects verified that the subjects were "high" on these low potency
marijuana cigarettes.
Kiplinger, Manno, Rodda, Forney, Haine, Ease, &
Richards (1971) conducted a randomized block, double-blind study designed to
establish a dose-response analysis of the THC content in marijuana using a
variety of behavioral and subjective effects measures. Marijuana cigarettes were
manufactured to deliver doses
of 0, 6.25, 12.5, 25, and 50 ?.g/kg of ?9-THC . Based on
an average 70 kg man, the total delivered doses of THC were 0, 0.43, 0.875,
1.75, and 3.5 mg. Based on the assumption of a 50% loss of THC from pyrolysis
and sidestream smoke these doses would be equivalent to smoking cigarettes
containing 0, 0.08%, 0.16%, 0.3%, and 0.7% THC containing hemp. The lower
concentrations of THC were used because these doses are found in the weaker
"hemp" or fiber type marijuana commonly grown in the United States.
All doses of THC, including the two lowest doses, increased the subjective
ratings on both the ARCI and Cornell Medical Indexes, produced heart-rate
increases, increased motoric decrements in pursuit meter, and produced
decrements in mental performance using the delayed auditory feedback test. Most
importantly, 80%
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