Research Index | Medline Index
Cannabis Research - set & setting, impurities and other problems with experiments
- Authors
- Ashton H, Golding J, Marsh VR, Millman JE, Thompson JW
- Title
- The seed and the soil: effect of dosage, personality and starting
state on the response to delta 9 tetrahydrocannabinol in man.
- Source
- British Journal of Clinical Pharmacology
- Date
- 1981 Nov
- Issue
- 12(5)
- Pages
- 705-20
- Abstract
- 1 The effects of two doses of delta 9THC (2.5 and 10 mg), delivered
by paced smoking of herbal cigarettes, on CNV magnitude, subjective
mood ratings and heart rate were studied in 20 subjects. 2 There
were highly significant interactions between drug dosage and
Extraversion and Neuroticism scores, so that the direction and
degree of response to the different doses of delta 9THC depended on
the personality characteristics of the subjects. 3 The effects of 9
mg delta 9THC and placebo, delivered in herbal cigarettes smoked
naturally, on smoking behaviour, subjective mood ratings, measures
of autonomic activity and auditory and visual cortical evoked
responses were compared in 12 subjects. 4 Smoking behaviour,
subjective 'high' rating and elevation of heart rates were the most
significant discriminators between drug and placebo. The latency of
some of the components of the visual evoked responses was also
increased by delta 9THC. 5 There was a significant correlation
between the effects of delta 9THC on skin conductance reactivity and
the basal (pre-drug) level, reactivity increasing after drug in
subjects with low basal reactivity and decreasing in those with high
basal levels. 6 Both experiments provided clear evidence of
dose-dependent biphasic stimulant and depressant actions of delta
9THC on both subjective and objective measures, and these effects
were influenced by the personality and the starting state of the
subjects.
- Authors
- Dalterio S, Bartke A, Mayfield D
- Title
- A novel female influences delta 9-THC effects on plasma hormone
levels in male mice.
- Source
- Pharmacology, Biochemistry & Behavior
- Date
- 1981 Aug
- Issue
- 15(2)
- Pages
- 281-4
- Abstract
- Exposure to delta 9-tetrahydrocannabinol (THC) (50 mg/kg) alters the
endocrine responsivity of male mice to female-related exteroceptive
stimuli. Exposure to a novel female prevents or delays the
THC-induced decrease in plasma testosterone (T) and luteinizing
hormone (LH) levels. These hormonal alterations are apparently not
due to the LH-releasing effects of female-related pheromonal or
tactile cues, since administration of luteinizing hormone releasing
factor (LRF) did not mimic the effects of a novel female on plasma T
levels in THC-treated males. Exposure to a much lower dose of THC
(0.5 mg/kg) did augment the LRF-induced increases in plasma T levels
suggesting a possible synergism between gonadotropins and THC on
androgen production. The present findings suggest that THC-induced
alterations in hormonal status may be influenced by complex social
or environmental factors.
- Authors
- Ungerleider JT, Andrysiak T
- Title
- Bias and the cannabis researcher.
- Source
- Journal of Clinical Pharmacology
- Date
- 1981 Aug-Sep
- Issue
- 21(8-9 Suppl)
- Pages
- 153S-158S
- Abstract
- This report focuses on several aspects of the "drug" cannabis in our
society: the historical notion of a chemical as a moral issue (i.e.,
good and evil) rather than a pharmacological one; the scientist as a
human being as well as a witting or unwitting influencer of social
policy; the statistical design and manipulation of research
consciously or unconsciously for fame and fortune (grants); the
research treatment "connection" as part of our drug abuse industrial
complex, a billion dollar a year industry; and the covert
governmental manipulation and distortion of cannabis (and other
drug) data.
- Authors
- Baumrind D
- Title
- Specious causal attributions in the social sciences: the
reformulated stepping-stone theory of heroin use as exemplar.
- Source
- Journal of Personality & Social Psychology
- Date
- 1983 Dec
- Issue
- 45(6)
- Pages
- 1289-98
- Abstract
- The claims based on causal models employing either statistical or
experimental controls are examined and found to be excessive when
applied to social or behavioral science data. An exemplary case, in
which strong causal claims are made on the basis of a weak version
of the regularity model of cause, is critiqued. O'Donnell and
Clayton claim that in order to establish that marijuana use is a
cause of heroin use (their "reformulated stepping-stone"
hypothesis), it is necessary and sufficient to demonstrate that
marijuana use precedes heroin use and that the statistically
significant association between the two does not vanish when the
effects of other variables deemed to be prior to both of them are
removed. I argue that O'Donnell and Clayton's version of the
regularity model is not sufficient to establish cause and that the
planning of social interventions both presumes and requires a
generative rather than a regularity causal model. Causal modeling
using statistical controls is of value when it compels the
investigator to make explicit and to justify a causal explanation
but not when it is offered as a substitute for a generative analysis
of causal connection.
- Authors
- Landrigan PJ, Powell KE, James LM, Taylor PR
- Title
- Paraquat and marijuana: epidemiologic risk assessment.
- Source
- American Journal of Public Health
- Date
- 1983 Jul
- Issue
- 73(7)
- Pages
- 784-8
- Abstract
- In March 1978, 13 (21 per cent) of 61 marijuana samples from the
southwestern United States were found to be contaminated with the
herbicide paraquat, a pulmonary toxin, in concentrations from 3 to
2,264 parts per million. The source of the contamination was an
aerial spraying program in Mexico, supported indirectly by United
States funds. To evaluate US exposure, a nationwide survey of the
paraquat content of confiscated marijuana was conducted. The survey
found 33 (3.6 per cent) of 910 marijuana specimens to contain
detectable paraquat. In states adjacent to Mexico (Census Region
VI), 23 (12.8 per cent) of 180 specimens were contaminated.
Combustion testing indicated that approximately 0.2 per cent of
paraquat on marijuana passes into smoke. From these data, we
projected that 100-200 marijuana smokers in Census Region VI would
be exposed by inhalation to 500 micrograms or more of paraquat per
year, a dose judged to represent a health hazard; nationally,
between 150 and 300 smokers were projected to have such exposure.
Another 6,000 persons in Region VI and 9,000 nationally were
projected to be at risk of exposure to between 100 and 499
micrograms of paraquat annually. The risk of paraquat exposure was
greatest among those smokers who make one large purchase of
marijuana per year. No clinical cases of paraquat poisoning were
recognized among marijuana smokers during these studies, but no
systematic national search for such cases was undertaken.
- Authors
- Kagen SL, Kurup VP, Sohnle PG, Fink JN
- Title
- Marijuana smoking and fungal sensitization.
- Source
- Journal of Allergy & Clinical Immunology
- Date
- 1983 Apr
- Issue
- 71(4)
- Pages
- 389-93
- Abstract
- The possible role of marijuana (MJ) in inducing sensitization to
Aspergillus organisms was studied in 28 MJ smokers by evaluating
their clinical status and immune responses to microorganisms
isolated from MJ. The spectrum of illnesses included one patient
with systemic aspergillosis and seven patients with a history of
bronchospasm after the smoking of MJ. Twenty-one smokers were
asymptomatic. Fungi were identified in 13 of 14 MJ samples and
included Aspergillus fumigatus, A. flavus, A. niger, Mucor,
Penicillium, and thermophilic actinomycetes. Precipitins to
Aspergillus antigens were found in 13 of 23 smokers and in one of 10
controls, while significant blastogenesis to Aspergillus was
demonstrated in only three of 23 MJ smokers. When samples were
smoked into an Andersen air sampler, A. fumigatus passed easily
through contaminated MJ cigarettes. Thus the use of MJ assumes the
risks of both fungal exposure and infection, as well as the possible
induction of a variety of immunologic lung disorders.
- Authors
- Ali SF, Newport GD, Scallet AC, Paule MG, Bailey JR, Slikker W Jr
- Title
- Chronic marijuana smoke exposure in the rhesus monkey. IV:
Neurochemical effects and comparison to acute and chronic exposure
to delta-9-tetrahydrocannabinol (THC) in rats.
- Source
- Pharmacology, Biochemistry & Behavior
- Date
- 1991 Nov
- Issue
- 40(3)
- Pages
- 677-82
- Abstract
- THC is the major psychoactive constituent of marijuana and is known
to produce psychopharmacological effects in humans. These studies
were designed to determine whether acute or chronic exposure to
marijuana smoke or THC produces in vitro or in vivo neurochemical
alterations in rat or monkey brain. For the in vitro study, THC was
added (1-100 nM) to membranes prepared from different regions of the
rat brain and muscarinic cholinergic (MCh) receptor binding was
measured. For the acute in vivo study, rats were injected IP with
vehicle, 1, 3, 10, or 30 mg THC/kg and sacrificed 2 h later. For the
chronic study, rats were gavaged with vehicle or 10 or 20 mg THC/kg
daily, 5 days/week for 90 days and sacrificed either 24 h or 2
months later. Rhesus monkeys were exposed to the smoke of a single
2.6% THC cigarette once a day, 2 or 7 days a week for 1 year.
Approximately 7 months after the last exposure, animals were
sacrificed by overdose with pentobarbital for neurochemical
analyses. In vitro exposure to THC produced a dose-dependent
inhibition of MCh receptor binding in several brain areas. This
inhibition of MCh receptor binding, however, was also observed with
two other nonpsychoactive derivatives of marijuana, cannabidiol and
cannabinol. In the rat in vivo study, we found no significant
changes in MCh or other neurotransmitter receptor binding in
hippocampus, frontal cortex or caudate nucleus after acute or
chronic exposure to THC. In the monkey brain, we found no
alterations in the concentration of neurotransmitters in caudate
nucleus, frontal cortex, hypothalamus or brain stem.(ABSTRACT
TRUNCATED AT 250 WORDS)
- Authors
- Elsohly MA, Little TL Jr, Hikal A, Harland E, Stanford DF, Walker L
- Title
- Rectal bioavailability of delta-9-tetrahydrocannabinol from various
esters.
- Source
- Pharmacology, Biochemistry & Behavior
- Date
- 1991 Nov
- Issue
- 40(3)
- Pages
- 497-502
- Abstract
- The bioavailability of delta-9-tetrahydrocannabinol (delta 9-THC)
from suppository formulations containing several polar esters was
studied. The esters tested were the hemisuccinate, N-formyl
alaninate, N-methyl carbamate, and methoxy acetate. These esters
were administered to monkeys in both lipophilic and hydrophilic
suppository bases, namely, Witepsol H15 and polyethylene glycol,
respectively. Each suppository contained a dose equivalent to 10 mg
delta 9-THC. Blood samples were analyzed for both delta 9-THC and
its carboxylic acid metabolite (ll-nor-delta 9-THC-9-COOH) using gas
chromatography/mass spectrometry. The data showed that, with the
exception of the hemisuccinate, no delta 9-THC or its metabolite was
detected in the blood samples using the Witepsol H15. Using
polyethylene glycol, low levels of delta 9-THC and its metabolite
were detected in blood for all esters tested. The levels, however,
were lower than those observed with delta 9-THC hemisuccinate using
Witepsol H15. Subsequent studies in the conscious dog using the
hemisuccinate in Witepsol H15 showed 67% bioavailability of delta
9-THC with a linear response in the dose range equivalent to 5-20 mg
of delta 9-THC. No significant bioavailability differences were
found when delta 9-THC hemisuccinate ester was administered in
various lipophilic bases (Hydrokote 25, Kaomel, Suppocire AIML, and
Witepsol H15).
- Authors
- ElSohly MA, Stanford DF, Harland EC, Hikal AH, Walker LA, Little TL Jr, Rider JN, Jones AB
- Title
- Rectal bioavailability of delta-9-tetrahydrocannabinol from the
hemisuccinate ester in monkeys.
- Source
- Journal of Pharmaceutical Sciences
- Date
- 1991 Oct
- Issue
- 80(10)
- Pages
- 942-5
- Abstract
- Oral administration of delta-9-tetrahydrocannabinal (delta 9-THC)
was shown to result in low and erratic bioavailability, while the
drug showed no bioavailability from various suppository
formulations. delta 9-THC-Hemisuccinate was formulated as a prodrug
for delta 9-THC in suppositories using Witepsol H15 base. The
bioavailability of delta 9-THC from this formulation was evaluated
in monkeys. The plasma levels of delta 9-THC and its metabolite
11-nor-delta 9-THC-9-COOH were determined using GC/MS analysis. The
calculated bioavailability of delta 9-THC from this formulation was
found to be 13.5%. Non-compartmental analysis of the plasma
concentration data using statistical moments showed the mean
residence time (MRT) for delta 9-THC in the body to be 3 h following
iv administration of delta 9-THC or its hemisuccinate ester (3.4 and
2.7 h, respectively), as compared with 5.8 h following rectal
administration of the delta 9-THC hemisuccinate. The observed rectal
bioavailability of delta 9-THC from suppositories containing the
hemisuccinate ester as a prodrug is of significant importance in
developing an alternative approach to oral administration of the
drug.
- Authors
- Hutchings DE, Dow-Edwards D
- Title
- Animal models of opiate, cocaine, and cannabis use. [Review]
- Source
- Clinics in Perinatology
- Date
- 1991 Mar
- Issue
- 18(1)
- Pages
- 1-22
- Abstract
- A traditional concern with drugs administered during pregnancy has
been teratogenicity or the production of gross structural
malformations. Beginning in the 1970s, it became increasingly
evident that the issue of drug safety and risk assessment went far
beyond structural defects. During the 1980s, the newly emerged
research specialty of "developmental toxicology" came to encompass a
wide range of adverse toxic outcomes that include not only birth
defects but also neurobehavioral and other functional effects as
well. Substances of use and abuse--the opiates, cocaine, and
cannabis--have come to exemplify a diverse group of compounds that
produce a broad spectrum of developmental outcomes. Unlike alcohol,
neither the use of heroin nor methadone during pregnancy is
associated with an increased risk of birth defects but both produce
a neonatal abstinence syndrome that can persist for as long as 6
months; follow-up to preschool years suggests possible risk of
attention deficit and problems of fine motor coordination.
Methodologic weaknesses of opiate animal models, especially with
respect of appropriate dosing schedules, have hampered meaningful
extrapolation of these studies to human risk assessment. Given the
renewed interest in methadone maintenance as an important
therapeutic intervention to reduce exposure to the human
immunodeficiency virus, better designed animal studies are needed
urgently to assess developmental risk, but these must incorporate
techniques that better model human pharmacokinetics. Animal models
of early cocaine exposure, driven by human reports of serious risk
to the fetus and newborn, have found reproductive hazard, risk of
neurobehavioral effects as well as altered CNS function. Whereas
animal studies need to explore routes of administration other than
sc and ig, particularly the volatilized form of cocaine, to date it
appears that the processes of somatic growth and morphogenesis in
rodents are not as sensitive to cocaine as is the functional
development of the CNS. Finally, animal studies of cannabis have
taught us some major methodologic and interpretive lessons for the
continuing development and refinement of animal models of drugs of
abuse. Of particular importance is that poorly controlled
experiments that do not adequately consider the confounding
influences of maternal toxicity, both prenatally and postnatally,
are likely to yield a high rate of false-positive results. This is
well illustrated by those studies of cannabis that antedated the
current concern for pair-feeding and surrogate fostering. Nearly all
of the studies that failed to include nutritional and fostering
controls found neurobehavioral effects that included changes in
activity as well as impairments in learning and memory.(ABSTRACT
TRUNCATED AT 400 WORDS)
- References
- 55
- Authors
- Mechoulam R, Devane WA, Breuer A, Zahalka J
- Title
- A random walk through a cannabis field. [Review]
- Source
- Pharmacology, Biochemistry & Behavior
- Date
- 1991 Nov
- Issue
- 40(3)
- Pages
- 461-4
- Abstract
- The present overview covers various aspects of research going on in
the Cannabis field in the Department of Natural Products at the
Hebrew University. In the first part we discuss, and try to explain,
the reason for the absence of the term Cannabis (and possibly also
opium) in the Old Testament. In the second part we bring evidence
that, contrary to widely held views, stereospecificity of
cannabinoid action is extremely high, and in certain cases almost
absolute. Previous results seem to have been due to impurities in
the samples tested. (+)-Delta-1-THC, (+)-delta-6-THC and
(+)-7-hydroxy-delta-6-THC, when purified sufficiently, exhibit
activity of about 1% of that of the natural (-) enantiomers. A new
labelled cannabinoid ligand has been prepared by catalytic reduction
of (-)-7-hydroxy-delta-6-THC dimethylheptyl. The equatorial C-1
epimer obtained binds to the cannabinoid receptor with a KI of 40
pM. This compound is one of the most active cannabinoids tested so
far for binding to the canabinoid receptor, and may become an
important tool in cannabinoid research.
- References
- 25
- Authors
- Gfroerer JC, Hughes AL
- Title
- The feasibility of collecting drug abuse data by telephone.
- Source
- Public Health Reports
- Date
- 1991 Jul-Aug
- Issue
- 106(4)
- Pages
- 384-93
- Abstract
- An evaluation was made of the use of telephone survey methods to
collect illicit drug use data. Using data from a national survey
that collects data by personal interviews, marijuana and cocaine use
prevalence rates among households with telephones and those without
were compared in order to assess coverage errors in telephone
surveys. Drug use rates were substantially higher among households
without telephones, with 24.9 percent of those living in households
without telephones reporting use of marijuana in the past year,
compared with only 9.4 percent of persons living in households with
telephones. Trends in drug use were divergent, with substantial
decreases in use occurring between 1985 and 1988 in households with
telephones, but not in those without. National prevalence patterns
and trends among households with telephone appear to be consistent
with national patterns and trends in the total household population,
because about 93 percent of the population lives in households with
telephones. However, surveys conducted by telephone were found to
produce underestimates of illicit drug use prevalence. In a 1988
national telephone survey, estimated rates of past year use were 5.2
percent for marijuana and 1.4 percent for cocaine. Comparable data
from a personal visit survey (including only households with
telephones and reedited and reweighted to control for differences in
data collection protocols) were 8.0 percent for marijuana and 3.1
percent for cocaine use. Comparisons with several other telephone
surveys collecting illicit drug use data showed similar results.
Based on these results, researchers are advised to use caution in
using telephone surveys to produce drug use prevalence estimates.
- Id Code
- 75196832
- Authors
- Constoe PF, Jones BC, Chin L
- Title
- Delta-9-tetrahydrocannabinol, EEG and behavior:the importance of
adaptation to the testing milieu.
- Source
- Pharmacology, Biochemistry & Behavior
- Date
- 1975 Mar-Apr
- Issue
- 3(2)
- Pages
- 173-7
- Abstract
- Delta-9-Tetrahydrocannabinol (delta-9-THC) in doses of 0.01, 0.05,
0.1, 0.5, and 1.0 mg/kg, i.v. was administered to adult rabbits
previously adapted to the testing chamber. Additionally, a group of
rabbits not adapted to any part of the testing regimen was
administered 1.0 mg/kg delta-9-THC. Cortical and hippocampal
electroencephalographs as well as postural and activity behaviors of
the unrestrained animals were recorded. In the adapted rabbits,
there were dose-related increased in cortical voltage output,
disruption of hippocampal theta rhythm and cortical polyspike
bursts. Behaviorally, there was a dose-related tendency for standing
and exploration to decrease, and at 0.5 and 1.0 mg/lh, delta-9-THC
produced sprawling. In the nonadapted rabbits, administration of 1.0
mg/kh of the drug caused EEG and behavioral stimulation followed by
depression of both, The results suggest that the behavioral actions
of cannabinols are largely dependent upon the animal's existing
state of arousal.
- Id Code
- 77209452
- Authors
- Smith RN, Vaughan CG
- Title
- The decomposition of acidic and neutral cannabinoids in organic
solvents.
- Source
- Journal of Pharmacy & Pharmacology
- Date
- 1977 May
- Issue
- 29(5)
- Pages
- 286-90
- Abstract
- High-pressure liquid chromatography was used to study (a) the
relative efficiencies of methanol, chloroform, light petroleum (B.P.
40-60 degrees) and methanol-chloroform (9:1) for extracting neutral
and acidic cannabinoids from cannabis resin; (b) the decomposition
patterns of the resulting solutions under various storage
conditions, and (c) the cannabinoid profile of a cross section
through a block of cannabis resin. The results show that (a)
methanol is the most effective extracting solvent of those tested;
(b) acidic cannabinoids in solution decompose in darkness by varying
amounts depending on the temperature, solvent, storage time and
particular cannabinoid; (c) neutral cannabinoids in solution are
relatively stable in darkness; (d) daylight causes appreciable
decomposition of both acidic and neutral cannabinoids in solution,
(e) the cannabinoid profile of a resin is complex with lower levels
of acidic material in the outer layers.
- Id Code
- 76217000
- Authors
- Fairbairn JW, Liebmann JA, Rowan MG
- Title
- The stability of cannabis and its preparations on storage.
- Source
- Journal of Pharmacy & Pharmacology
- Date
- 1976 Jan
- Issue
- 28(1)
- Pages
- 1-7
- Abstract
- Solutions of pure cannabinoids, nine samples of herbal and two of
resin cannabis (one freshly prepared) were stored in varying
conditions for up to 2 years. Exposure to light (not direct
sunlight) was shown to be the greatest single factor in loss of
cannabinoids especially in solutions, which should therefore be
protected from light during analytical and phytochemical operations.
Previous claims that solutions in ethanol were stable have not been
substantiated. The effect of temperature, up to 20 degrees, was
insignificant but air oxidation did lead to significant losses.
These could be reduced if care was taken to minimize damage to the
glands which act as "well filled, well closed containers". Loss of
tetrahydrocannabinol after exposure to light does not lead to an
increase in cannabinol, but air oxidation in the dark does. It is
concluded that carefully prepared herbal or resin cannabis or
extracts are reasonably stable for 1 to 2 years if stored in the
dark at room temperature.
- Id Code
- 80008763
- Authors
- Carney JM, Balster RL, Martin BR, Harris LS
- Title
- Effects of systemic and intraventricular administration of
cannabinoids on schedule-controlled responding in the squirrel
monkey.
- Source
- Journal of Pharmacology & Experimental Therapeutics
- Date
- 1979
Sep
- Issue
- 210(3)
- Pages
- 399-404
- Abstract
- The effects of a number of cannabinoids in squirrel monkeys trained
to respond on a chain fixed-interval fixed-ratio schedule of food
presentation were determined after intraperitoneal (i.p.) and
intraventricular (i.v.t.) administration. The order of potency was
(+/-)-9-nor-9 beta-OH hexahydrocannabinol, 11-OH-delta
9-tetrahydrocannabinol, delta 9-tetrahydrocannabinol (delta 9-THC),
cannabinol and cannabidiol. (+/-)-9-Nor-9
alpha-OH-hexahydrocannabinol was inactive at doses up to 3 mg/kg
i.p. and 0.1 mg/kg i.v.t. Although the order of potency was the same
by both routes of administration, the i.v.t./i.p. potency ratio
differed markedly. This demonstrates the importance of route of
administration in assessing structure-activity relationships of
cannabinoids and suggests that differences in penetration to the
central nervous system may be an important determinant of behavioral
activity. Although 11-OH-delta 9-THC was more potent than the parent
compound delta 9-THC by both routes, the potency difference was less
after i.v.t. administration. It was also demonstrated that metabolic
conversion of [3H:delta 9-THC does not take place in squirrel monkey
brain when administered i.v.t. which could account for the direct
i.v.t. effects of delta 9-THC. These observations suggest that
metabolic conversion of delta 9-THC in the liver is not necessary
for its behavioral effects.
- Id Code
- 78031197
- Authors
- Matsuyama S, Jarvik L
- Title
- Effects of marihuana on the genetic and immune systems. [Review]
- Source
- NIDA Research Monograph
- Date
- 1977 Jul
- Issue
- (14)
- Pages
- 179-93
- Abstract
- With the continued widespread abuse of marihuana and the potential
use of marihuana as a therapeutic agent being widely discussed, it
becomes important to assess the effects of marihuana and other
cannabis preparations on the immune mechanisms and the genetic
material. This chapter integrates recent findings with those in the
Fifth Marihuana and Health Report (1975) to provide a wiser data
base from which conclusions may be drawn. Animal studies and human
studies are considered separately because it is not known to what
extent, if at all, results from animal studies can be directly
extrapolated to man.
- References
- 66
- Id Code
- 80021697
- Authors
- Narayanaswami K, Golani HC, Bami HL, Dau RD
- Title
- Stability of Cannabis sativa L. samples and their extracts, on
prolonged storage in Delhi.
- Source
- Bulletin on Narcotics
- Date
- 1978 Oct-Dec
- Issue
- 30(4)
- Pages
- 57-69
- Abstract
- The percentage rate of change into cannabinoids (Cannabidiol [CBD],
tetrahydrocannabinol [THC] and cannabinol [CBN]) was higher in
cannabis samples than in the extracts. This is probalby due to the
decomposition of acids into corresponding neutral cannabinoids under
the conditions of storage. Previous claims that CBD content in plant
material is relatively constant are not substantiated by our
results. There was a 1.0-2.5-fold increase in CBD content in plant
material compared with the extracts. However, the fact that there
was no appreciable increase in CBD/CBN content in the stored
extracts of the same samples supports the view that the step-wise
extraction does not bring the acids into the final extract pure
delta 9THC decomposed at a rate of 41 per cent per year under
tropical storage conditions. The delta 9THC content decreased in the
samples and equally in the extracts though 100 per cent conversion
of THC to CBN does not take place. The higher CBN content found in
extracts than that expected by the conversion THC to CBN is a result
of metabolic conversion.
- Id Code
- 80021696
- Authors
- Turner CE, Cheng PC, Torres LM, Elsohly MA
- Title
- Detection and analysis of paraquat in confiscated marijuana samples.
- Source
- Bulletin on Narcotics
- Date
- 1978 Oct-Dec
- Issue
- 30(4)
- Pages
- 47-56
- Abstract
- A spectrophotometric method used to test for paraquat in 160
confiscated marijuana samples is described. Twenty of these samples
(12.5 per cent) tested positive for paraquat. Nine confiscated hash
oil samples tested negative. The identification of paraquat was
proven by isolation, chromatography, and spectral methods. The
cannabinoids in paraquat positive Cannabis samples were analysed.
- Id Code
- 80071229
- Authors
- Russell JA, Bond CR
- Title
- Beliefs among college students on settings and emotions conducive to
alcohol and marijuana use.
- Source
- International Journal of the Addictions
- Date
- 1979 Oct
- Issue
- 14(7)
- Pages
- 977-86
- Abstract
- Two hundred college student alcohol and marijuana users rated their
desire to drink alcohol and desire to smoke marijuana in or after
different settings shown via color photographic slides. Contrary to
the compensation hypothesis (that these drugs are used to escape
from unpleasant circumstances), desire for both alcohol and
marijuana was greater both in and after more pleasant settings than
unpleasant ones. These results were more consistent with an
amplification hypothesis, that alcohol and marijuana intensify
emotions already present.
- Id Code
- 79137293
- Authors
- Martin P, Consroe P
- Title
- Tolerance to delta9-tetrahydrocannabinol in adapted and nonadapted
rabbits.
- Source
- Pharmacology, Biochemistry & Behavior
- Date
- 1978 Dec
- Issue
- 9(6)
-
Pages
- 753-8
- Abstract
- Two groups of New Zealand white rabbits, one which had been adapted
to the testing chamber and one which had not been adapted to the
testing chamber, were given delta9-tetrahydrocannabinol (delta9-THC;
0.5 mg/kg, IV) daily for 12 days. During vehicle control and on the
first and last day of delta9-THC administration,
electroencephalograms (EEG's) were recorded from the motor cortex
and hippocampus, while standing, sprawling and behavioral activity
were recorded concurrently. The results showed that tolerance to the
behavioral and EEG effects of delta9-THC occurs in rabbits and that
acute and chronic effects produced by delta9-THC are influenced by
environmental factors.
- Id Code
- 79066919
- Authors
- Stewart J, Nielsen PJ, Neidig PH
- Title
- An investigation of procedures reported to increase potency of
marijuana: a chemical analysis and psychological interpretation.
- Source
- International Journal of the Addictions
- Date
- 1978 Jul
- Issue
- 13(5)
- Pages
- 831-7
- Abstract
- Three basic procedures from the "underground press" for increasing
the potency of marijuana were tested quantitatively: Black Merta,
Dry Ice, and isopropanol--water extraction. In all methods there was
not significant change in THC, CBN, or CBD content before and after
treatment. The persistence of procedures which have no measurable
effect on the chemical properties of the drug is presented as
additional evidence for the importance of psychological factors in
perceived drug effects.
- Id Code
- 85153165
- Authors
- Schurr A
- Title
- Marihuana: much ado about THC. [Review]
- Source
- Comparative Biochemistry & Physiology - C: Comparative Pharmacology &
Toxicology
- Date
- 1985
- Issue
- 80(1)
- Pages
- 1-7
- Abstract
- The availability of delta 1-THC, the major psychoactive component of
marihuana, in pure form offered an opportunity for better
understanding of the mechanism of action of this drug. Two decades
after the isolation of delta 1-THC its mode of action is still
obscure despite the enormous amount of research invested in it.
Studying cannabis content as a whole offers a different approach for
better understanding of this ancient weed and its effects.
- References
- 75
- Id Code
- 86036617
- Authors
- Morningstar PJ
- Title
- Thandai and chilam: traditional Hindu beliefs about the proper uses
of Cannabis.
- Source
- Journal of Psychoactive Drugs
- Date
- 1985 Jul-Sep
- Issue
- 17(3)
- Pages
- 141-65
- Abstract
- Hindu beliefs about appropriate use of cannabis illustrate the
capacity of cultural systems to order and direct the course of
complex phenomenal events. Cannabis manifests diverse and
contradictory effects. These depend not only on dose, frequency and
route of administration, but also on subjective and cultural
contexts (e.g., Pihl, Shea & Costa 1979). It may very well be that
the contradictory results of modern research investigations on
cannabis stem from the intricacy of these interactions. Given the
current state of the art, paradigms of research methodology may very
well be inadequate to develop an understanding of such a paradoxical
drug. The Hindu cultural system, on the other hand, accommodates the
ambiguities of cannabis through its own complex nature. It provides
diverse niches through which antithetical effects of the drug are
expressed. Cannabis is said to both interfere with motivation to
work and facilitate it. A closer examination reveals that these
actions are probably related to the way in which this motivation
toward action is defined, and the level of use of the drug. While
cannabis appears to interfere with execution of highly complex tasks
and the long-range planning that accompanies them, it may facilitate
concentrated focus on repetitive endeavors. In some commonsense way,
it may be quite simply that it changes a user's sense of time and
the span of the present as well as the sense of relative importance
of present and future. So long as an individual is under the
influence of this effect (and living in the context that s/he has
structured as a result of it), the urgency of accomplishment in the
Western sense is diminished. The Hindu belief system accommodates
this by prescribing use in such a way that this effect becomes
beneficial. A key factor is that low potency preparations (bhang,
thandai) are available. It allows individuals with complex life
tasks, goals and obligations to indulge in moderation. The drug is
also taken in a ritualized context, facilitating concentration and
relaxation. It is taken at times, such as in the evening or on
holidays, in which focus on the immediate present is a welcome
change. Use of the more potent preparations (ganja, charas) is not
condoned for this group. Above all, moderation is enjoined and
popular folk belief warns of the potential problems of excess. Ganja
and charas are regarded more ambivalently as poisons or
semipoisons.(ABSTRACT TRUNCATED AT 400 WORDS)
- Id Code
- 91130229
- Authors
- Harvey DJ, Brown NK
- Title
- In vitro metabolism of delta-11-tetrahydrocannabinol in the mouse,
rat, guinea pig, rabbit, hamster, gerbil and cat.
- Source
- Comparative Biochemistry & Physiology - C: Comparative Pharmacology &
Toxicology
- Date
- 1990
- Issue
- 96(1)
-
Pages
- 65-9
- Abstract
- 1. Liver microsomes were prepared from rats, rabbits, guinea pigs,
hamsters, gerbils, a cat and three strains of mice, and were
incubated with delta-11-tetrahydrocannabinol (delta-11-THC). The
extracted metabolites were separated by chromatography on Sephadex
LH-20 and examined by gas chromatography and combined gas
chromatography/mass spectrometry. 2. Eleven metabolites were
identified; these were formed by aliphatic hydroxylation of all
positions of the pentyl chain, allylic hydroxylation at C-10 and C-8
(alpha and beta), and by the epoxide-diol pathway. 3. The ratio of
the metabolites varied considerably between the species. Mice and
rats favoured hydroxylation at C-8-alpha with very little
hydroxylation of the pentyl chain. 4. In the guinea pig, however,
hydroxylation of the pentyl chain, particularly at C-4', produced
the major metabolites; very little hydroxylation occurred at C-8. 5.
Side-chain hydroxylation was also favoured by the gerbil. 6. In the
cat and hamster, 8-beta-hydroxylation was by far the major metabolic
route, accounting, in the cat, for nearly 70% of the recovered
metabolites. 7. The rabbit, on the other hand, favoured the
epoxide-diol pathway with over 70% of the recovered metabolites
being accounted for by the 9,11-dihydro-diols. 8. The results
emphasise the need to make appropriate choices of animal models for
metabolic and toxicological studies in humans.
- Id Code
- 91061684
- Authors
- Allen RR, Slikker W Jr, Paule MG
- Title
- Repeated measures designs in behavioral toxicology: application to
chronic marijuana smoke exposure.
- Source
- Neurotoxicology & Teratology
- Date
- 1990 Sep-Oct
- Issue
- 12(5)
- Pages
- 441-8
- Abstract
- This paper discusses the application of repeated measures methods in
the statistical analysis of an experiment in behavioral toxicology.
The chronic marijuana smoke exposure study conducted at the National
Center for Toxicological Research is used for an example of the
types of problems that one encounters in analyzing these types of
studies. In particular, the standard univariate analysis most
frequently used for repeated measures analyses has some very
restrictive assumptions on the form of the covariance matrices.
These assumptions are not met in the example discussed and are
rarely met in many other problems. Other possible models for
analyzing repeated measures when these assumptions are not met are
presented and discussed. Other problems specific to the chronic
marijuana smoke exposure study that may occur in similar type
studies are presented. These include pooling the experimental units
into groups with comparable baselines, choosing a function of the
measures to be analyzed, dealing with a large data set with many
observation times and missing data, unequal group sizes and
different designs for different subsets of the experimental animals.
The standard univariate repeated measures analysis was chosen to
analyze the data even though the violations of the covariance
assumptions may lead to finding differences that do not exist (Type
I or false-positive errors), since the other methods presented also
had covariance assumptions that were not met or had low power. Use
of Bonferroni-type multiple comparisons on the single degree of
freedom contrasts of interest hopefully reduced the chances of these
false-positive results.
- Id Code
- 95175751
- Authors
- Kamien JB, Bickel WK, Hughes JR, Higgins ST, Smith BJ
- Title
- Drug discrimination by humans compared to nonhumans: current status
and future directions. [Review]
- Source
- Psychopharmacology
- Date
- 1993
- Issue
- 111(3)
- Pages
- 259-70
- Abstract
- In drug discrimination (DD) procedures, behavior is differentially
reinforced depending on the presence or absence of specific drug
stimuli. The DD paradigm has been widely adopted by behavioral
pharmacologists because of its specificity of stimulus control,
concordance with drug action at cellular levels and its use as a
preclinical model of subject-rated effects in humans. With the
successful extension of DD to humans, a comparison of human and
nonhuman DD will help place each in the context of the other.
Twenty-eight studies of DD in humans are reviewed, including studies
of amphetamine, opioid, benzodiazepine, caffeine, nicotine,
marijuana and ethanol discriminative stimuli. Comparison of
procedures between studies in humans and nonhumans reveals a common
tradition, except the use of instructions appears to facilitate
greatly DD acquisition in humans. Findings were qualitatively
similar between humans and nonhumans. Potency relationships were
quantitatively similar between humans and most, but not all, other
species. Areas of human DD needing additional empirical evaluation
include the influence of instructions, the effects of training dose
and the effects of antagonists. Additionally, antihistamines,
barbiturates, nicotine and marijuana are under-represented in human
DD.
- References
- 128
- Id Code
- 89244423
- Authors
- Chait LD, Pierri J
- Title
- Some physical characteristics of NIDA marijuana cigarettes.
- Source
- Addictive Behaviors
- Date
- 1989
- Issue
- 14(1)
- Pages
- 61-7
- Abstract
- Marijuana cigarettes of three different potencies (0.0%, 1.4% and
2.7% delta-9-tetrahydrocannabinol (THC) content) provided by the
National Institute on Drug Abuse (NIDA) were compared on a variety
of characteristics, including physical appearance, weight, burn
rate, and deliveries of total particulate matter and carbon
monoxide. Significant differences between the different potency
cigarettes were obtained on most measures. These differences could
be relevant to the design and interpretation of
pharmacologic/toxicologic and behavioral studies conducted with
these cigarettes. The possible basis for these observed differences,
methods for minimizing some of them, and other potential problems
related to the use of NIDA marijuana cigarettes are discussed.
- Id Code
- 88312094
- Authors
- Samara E, Bialer M, Mechoulam R
- Title
- Pharmacokinetics of cannabidiol in dogs.
- Source
- Drug Metabolism & Disposition
- Date
- 1988 May-Jun
- Issue
- 16(3)
- Pages
- 469-72
- Abstract
- Cannabidiol (CBD) is one of the major nonpsychoactive cannabinoids
produced by Cannabis sativa L. Recent studies have shown that CBD
has a high protective index, comparable to that of phenobarbital and
phenytoin. Because CBD has been reported to possess both
anticonvulsant and antiepileptic activity, its pharmacokinetics were
studied in dogs after the administration of two iv doses (45 and 90
mg) and one oral dose (180 mg) to dogs. After iv administration, CBD
was rapidly distributed, followed by a prolonged elimination. It has
a terminal half-life of 9 hr. CBD plasma levels declined in a
triphasic fashion. The total body clearance of CBD was 17 liters/hr
(after the 45-mg dose) and 16 liters/hr (after the 90-mg dose). This
clearance value, after its normalization to blood clearance using
mathematical equations, approaches the value of the hepatic blood
flow; the extraction ratio in the liver is 0.74. CBD was observed to
have a large volume of distribution, approximately 100 liters. In
the dose range of 45 to 90 mg, the increase in the AUC was
proportional to the dose, a fact that indicates that the
pharmacokinetic profile of CBD in this dose range was not dose
dependent. In three of the six dogs studied, CBD could not be
detected in the plasma after oral administration. In the other
three, the oral bioavailability ranged from 13 to 19%. The results
of this study show that CBD is barely absorbed after oral
administration to dogs. This low bioavailability may be due to a
first pass effect.
- Id Code
- 88230169
- Authors
- Formukong EA, Evans AT, Evans FJ
- Title
- Inhibition of the cataleptic effect of tetrahydrocannabinol by other
constituents of Cannabis sativa L.
- Source
- Journal of Pharmacy & Pharmacology
- Date
- 1988 Feb
- Issue
- 40(2)
- Pages
- 132-4
- Abstract
- Tetrahydrocannabinol (THC) induced catalepsy in mice, whereas a
cannabis oil (6.68% w/w THC), four cannabinoids and a synthetic
mixture did not. Cannabinol (CBN) and olivetol inhibited THC-induced
catalepsy in the mornings and the evenings, but cannabidiol (CBD)
exhibited this effect only in the evenings. A combination of CBN and
CBD inhibited THC-induced catalepsy equal to that of CBN alone in
the mornings, but this inhibition was greater than that produced by
CBN alone in the evenings.
- Id Code
- 89107431
- Authors
- Jrbe TU, Hiltunen AJ, Mechoulam R, Srebnik M, Breuer A
- Title
- Separation of the discriminative stimulus effects of stereoisomers
of delta 2- and delta 3-tetrahydrocannabinols in pigeons.
- Source
- European Journal of Pharmacology
- Date
- 1988 Nov 8
- Issue
- 156(3)
- Pages
- 361-6
- Abstract
- Pigeons, trained to discriminate between the presence or absence of
delta 1-tetrahydrocannabinol (THC) (I) (0.56 mg/kg), were tested
with (1S,4R)-delta 2-THC (II) (1-17.5 mg/kg), with the C-1 epimers
of (4R)-delta 2-THC acetate, namely (1S,4R)-delta 2-THC acetate
(IIIA) (3-17.5 mg/kg) and (1R,4R)-delta 2-THC acetate (IIIB) (1-17.5
mg/kg) and with the enantiomers of delta 3-THC acetate, namely
(1S)-delta 3-THC acetate (IVA) (1-10 mg/kg) and (1R)-delta 3-THC
acetate (IVB) (3-30 mg/kg). The results indicated that (I) was
considerably more potent than any of the other compounds evaluated
(ED50 of compound I = 0.18 and 0.25 mg/kg at the two post-injection
intervals examined, 90 and 270 min, respectively). Furthermore, of
the two delta 2-THC acetates, compound (IIIB) was active whereas
compound (IIIA) was not in comparable doses. The parent phenol of
compound (IIIA), namely (II), was also inactive. Comparison of the
pair of enantiomers, (IVA) and (IVB), showed the former to be
significantly more potent than the latter. We have thus shown that
the delta 1-THC-like cue properties are separated in the
stereoisomers of delta 2- and delta 3-THC.
- Id Code
- 89070547
- Authors
- Reichman M, Nen W, Hokin LE
- Title
- Delta 9-tetrahydrocannabinol increases arachidonic acid levels in
guinea pig cerebral cortex slices.
- Source
- Molecular Pharmacology
- Date
- 1988 Dec
- Issue
- 34(6)
- Pages
- 823-8
- Abstract
- Several studies have shown that the major psychoactive component in
marihuana, (-)-(trans)-delta 9-tetrahydrocannabinol (THC), increases
the level of unesterified arachidonic acid (AA) in non-neural cells
in culture. Little is known, however, about the effects of THC on AA
metabolism in the mammalian brain. In the present study, slices from
guinea pig brain cortex were prelabeled with [14C]AA, and the
effects of THC and other cannabinoids on the disposition of
esterified and unesterified [14C]AA were measured. Incubation of
prelabeled cortical slices with THC rapidly increased free [14C]AA
levels in a dose-dependent and saturable manner. A maximal increase
of over 4-fold was elicited by 32 microM THC, with the half-maximal
response occurring at 8.0 microM. Comparison of the potencies of
several other cannabinoids revealed that the inactive stereoisomer
of THC [(+)-THC] was equipotent with the naturally occurring isomer
in increasing unesterified [14C]AA levels. The relative rank-order
of potencies in the cannabinoid series we examined were (-)-THC =
(+)-THC greater than cannabinol greater than delta 8-THC greater
than cannabidiol. We also measured cannabinoid-induced changes in
the disposition of esterified [14C]AA in the neutral lipids and
phospholipids of brain cortex slices. After incubation with 8 microM
THC for 1 hr, the radioactivity in triacylglycerols was reduced by
over one third. The loss of esterified [14C] AA from
triacylglycerols accounted for less than 20% of the THC-induced rise
in free [14C]AA; the remainder was accounted for by losses in the
radioactivity contained in the phospholipid fraction, particularly
from phosphatidylinositol. The loss in radioactivity from
phosphatidylinositol alone accounted for over one half of the
THC-induced rise in unesterified [14C]AA. The results of the present
study indicate that in brain, as in extra-neural cells in culture,
cannabinoids increase unesterified AA levels; however, the relative
potencies of the cannabinoids we examined in increasing AA levels do
not correlate well with their in vivo psychoactive potencies.
- Id Code
- 88177030
- Authors
- O'Neal MF, Means LW, Porter JH, Rosecrans JA, Mokler DJ
- Title
- Rats that acquire a THC discrimination more rapidly are more
sensitive to THC and faster in reaching operant criteria.
- Source
- Pharmacology, Biochemistry & Behavior
- Date
- 1988 Jan
- Issue
- 29(1)
- Pages
- 67-71
- Abstract
- Male Sprague-Dawley rats were trained to discriminate
delta-9-tetrahydrocannabinol (THC) from saline in a two-lever
operant task using successive training criteria. Untreated animals
were first shaped to barpress for a milk reward with one lever
available. As each animal reached criterion the second lever was
installed, the first lever was removed, and the animal was treated
with 3.0 mg/kg THC 30 min prior to barpress training. When criterion
on the second lever was reached the rats were trained to
discriminate THC from vehicle injections with both levers available.
Following acquisition of the discrimination, test doses of THC at
0.00, 0.375, 0.75, 1.5 and 3.0 mg/kg revealed that the half of the
24 rats who reached criterion (STC) more rapidly exhibited
significantly greater sensitivity to THC at the 0.75 mg/kg test dose
than did the 12 slow-learner rats; the former group generated an
ED50 of 0.77 mg/kg, whereas the ED50 for the later group was 1.63
mg/kg. The fast learners acquired both the initial barpress response
and the discrimination more rapidly than did slow-learners. Results
suggest that some animals are inherently more sensitive to THC and
faster in meeting learning criteria.
- Id Code
- 89143685
- Authors
- Fischman MW, Foltin RW, Brady JV
- Title
- Human drug taking under controlled laboratory conditions.
- Source
- NIDA Research Monograph
- Date
- 1988
- Issue
- 84
- Pages
- 196-211
- Abstract
- The data presented point to the importance of studying drug effects
under the conditions in which those drugs are taken outside of the
laboratory. Interactions between the reinforcing and other direct
effects of these drugs, as well as their interactions with ongoing
environmental events, can only be evaluated under such conditions.
Tolerance to cocaine's effects which can lead to a potential for
increased toxicity, the regularity of both cocaine and marijuana
self-administration under both stable and varying environmental
conditions, and the regulation of caloric content of food all are
important factors in understanding (and therefore being able to
manipulate) substance use and abuse. These data also support the
utility of a residential research facility for the investigation of
substance use under conditions that approximate those in which
people live outside of the laboratory. This unique laboratory,
designed for continuous observation of human behavior over extended
periods of time, provides a carefully controlled research
environment with flexibility for establishing a range of subject
behaviors and recording both individual and social behavior
patterns. We can study regulation both within a day and over days,
assessing the effects of experimental manipulations on the
patterning of self-administration behavior. The design of such
studies is a logical extension of those reported in the animal
laboratory as well as those carried out in a more traditional human
behavioral pharmacology laboratory.
- Id Code
- 88283274
- Authors
- Hamadeh R, Ardehali A, Locksley RM, York MK
- Title
- Fatal aspergillosis associated with smoking contaminated marijuana,
in a marrow transplant recipient.
- Source
- Chest
- Date
- 1988 Aug
- Issue
- 94(2)
- Pages
-
432-3
- Abstract
- A 34-year-old man presented with pulmonary aspergillosis on the 75th
day after marrow transplant for chronic myelogenous leukemia. The
patient had smoked marijuana heavily for several weeks prior to
admission. Cultures of the marijuana revealed Aspergillus fumigatus
with morphology and growth characteristics identical to the organism
grown from open lung biopsy specimen. Despite aggressive antifungal
therapy, the patient died with disseminated disease. Physicians
should be aware of this potentially lethal complication of marijuana
use in compromised hosts.
- Id Code
- 86233682
- Authors
- Martin BR
- Title
- Cellular effects of cannabinoids. [Review]
- Source
- Pharmacological Reviews
- Date
- 1986 Mar
- Issue
- 38(1)
- Pages
- 45-74
- Abstract
- The many studies that have been included in this review suggest that
cannabinoids have ubiquitous effects on biological systems. These
results also underscore the intensity to which cannabinoids have
been studied. While there are numerous reasons for the prodigious
amount of cannabinoid research, a major stimulus has been the desire
to identify a specific biochemical event or pathway that is
responsible for the expression of delta 9-THC's unique
psychoactivity. It is the hope that delta 9-THC, as with all
centrally acting drugs, might serve as an important tool for
achieving a better understanding of the central nervous system. As
discussed in this review, the psychoactivity of cannabinoids might
best be described as a composite of numerous effects. If that is
indeed the case, then it would seem logical that these centrally
mediated effects do not arise from a single biochemical alteration,
but rather from multiple actions. Of course, a major problem arises
when one attempts to establish a relationship between cause and
effect when multiple mechanisms and effects are involved. An initial
approach to reducing the complexity of elucidation of mechanism of
action should involve attempts to distinguish those cannabinoid
actions which result in specific effects (psychoactivity) from those
which produce non-psychoactive effects (such as general depression).
There are several fundamental principles that can be used to assess
specificity, including concentration or dose of the drug that is
required to produce a given effect. Low doses of delta 9-THC are
capable of producing the psychoactivity that is unique to
cannabinoids, whereas higher doses may produce effects that are both
specific and nonspecific for cannabinoids. Unfortunately,
establishing this basic tenet for delta 9-THC has proven to be
difficult. It has not been possible to establish the concentration
of delta 9-THC at its site of action that is necessary to produce a
given pharmacological effect. While it is a simple matter to measure
the concentration of cannabinoids in either a whole tissue or an
incubation medium, the hydrophobicity of cannabinoids dramatically
affects their affinity for, and hence concentration in, the
biochemical components of the tissue. If the concentration of delta
9-THC could be measured at its site of action, then the relevance of
many of its pharmacological effects could be adequately determined.
Two possible mechanisms by which cannabinoids might produce
psychoactivity are membrane perturbation and receptor interactions,
and indeed, both mechanisms have received considerable
attention.(ABSTRACT TRUNCATED AT 400 WORDS)
- References
- 289
- Id Code
- 86203947
- Authors
- Hiltunen AJ, Jarbe TU
- Title
- Interactions between delta 9-tetrahydrocannabinol and cannabidiol as
evaluated by drug discrimination procedures in rats and pigeons.
- Source
- Neuropharmacology
- Date
- 1986 Feb
- Issue
- 25(2)
- Pages
- 133-42
- Abstract
- Animals (rats and pigeons) were trained to discriminate between the
presence and absence of delta 9-THC; the training doses were,
respectively: 0.56 mg/kg (pigeons) and 3.0 mg/kg (rats). Once the
drug discrimination was mastered, the pigeons were tested repeatedly
after a single intramuscular (i.m.) injection of delta 9-THC (0.56
mg/kg) at the following intervals 0.5, 1.5, 4.5 and 9 hr after the
injection. These results were compared with data from a separate
procedure, i.e. where the various intervals after injection were
examined only once per injection and both procedures yielded
essentially the same outcome. Thus, less than 50% appropriate
responding to THC was observed at 0.5 and 9 hr after injection,
whereas greater than 90% responding to THC occurred at 1.5 and 4.5
hr. The two procedures have previously been compared in rats (Jarbe,
Swedberg and Mechoulam, 1981). The repeated tests procedure was then
used to evaluate combinations of delta 9-THC and cannabidiol in both
species. Cannabidiol prolonged the cue effects of 1 mg/kg of delta
9-THC (intraperitoneal route of administration) in rats but did not
change the time-effect curve for delta 9-THC in pigeons (dose range
examined: 0.10--0.56 mg/kg); the challenge doses of cannabidiol
were, respectively: 30.0 mg/kg (i.p.) and 17.5 mg/kg (i.m.). The
rate of responding did not differ in tests with combinations of
delta 9-THC and cannabidiol as compared to delta 9-THC given alone
in pigeons. Subcutaneously administered 3-PPP, a dopamine
pre-synaptic blocker, did not induce responding appropriate for
delta 9-THC in rats.
- Id Code
- 86233680
- Authors
- Hollister LE
- Title
- Health aspects of cannabis. [Review]
- Source
- Pharmacological Reviews
- Date
- 1986 Mar
- Issue
- 38(1)
- Pages
- 1-20
- Abstract
- Marijuana seems firmly established as another social drug in Western
countries, regardless of its current legal status. Patterns of use
vary widely. As with other social drugs, the pattern of use is
critical in determining adverse effects on health. Perhaps the major
area of concern about marijuana use is among the very young. Using
any drug on a regular basis that alters reality may be detrimental
to the psychosocial maturation of young persons. Chronic use of
marijuana may stunt the emotional growth of youngsters. Evidence for
an amotivational syndrome is largely based on clinical reports;
whether marijuana use is a cause or effect is uncertain. A marijuana
psychosis, long rumored, has been difficult to prove. No one doubts
that marijuana use may aggravate existing psychoses or other severe
emotional disorders. Brain damage has not been proved. Physical
dependence is rarely encountered in the usual patterns of social
use, despite some degree of tolerance that may develop. The
endocrine effects of the drug might be expected to delay puberty in
prepubertal boys, but actual instances have been rare. As with any
material that is smoked, chronic smoking of marijuana will produce
bronchitis; emphysema or lung cancer have not yet been documented.
Cardiovascular effects of the drug are harmful to those with
preexisting heart disease; fortunately the number of users with such
conditions is minimal. Fears that the drug might accumulate in the
body to the point of toxicity have been groundless. The potential
deleterious effects of marijuana use on driving ability seem to be
self-evident; proof of such impairment has been more difficult. The
drug is probably harmful when taken during pregnancy, but the risk
is uncertain. One would be prudent to avoid marijuana during
pregnancy, just as one would do with most other drugs not essential
to life or well-being. No clinical consequences have been noted from
the effects of the drug on immune response, chromosomes, or cell
metabolites. Contamination of marijuana by spraying with defoliants
has created the clearest danger to health; such attempts to control
production should be abandoned. Therapeutic uses for marijuana, THC,
or cannabinoid homologs are being actively explored. Only the
synthetic homolog, nabilone, has been approved for use to control
nausea and vomiting associated with cancer chemotherapy.(ABSTRACT
TRUNCATED AT 400 WORDS)
- References
- 185
- Id Code
- 95251803
- Authors
- Parker LA, Gillies T
- Title
- THC-induced place and taste aversions in Lewis and Sprague-Dawley
rats.
- Source
- Behavioral Neuroscience
- Date
- 1995 Feb
- Issue
- 109(1)
- Pages
- 71-8
- Abstract
- The hedonic properties of delta-9-tetrahydrocannabinol (THC) were
assessed in place and taste conditioning paradigms in both Lewis and
Sprague-Dawley rat strains. THC produced place avoidance, taste
avoidance, and aversive taste reactivity responses in both strains.
The Lewis strain displayed more aversive taste reactions and a
stronger taste avoidance when conditioned with lower doses of THC
than did the Sprague-Dawley strain of rats. THC is an anomalous drug
of abuse that appears to be aversive to rats when assessed by these
measures.
- Id Code
- 95156259
- Authors
- Fride E, Barg J, Levy R, Saya D, Heldman E, Mechoulam R, Vogel Z
- Title
- Low doses of anandamides inhibit pharmacological effects of delta
9-tetrahydrocannabinol.
- Source
- Journal of Pharmacology & Experimental Therapeutics
- Date
- 1995
Feb
- Issue
- 272(2)
- Pages
- 699-707
- Abstract
- It has been shown previously that the endogenous cannabinoid
receptor ligand arachidonylethanolamide (anandamide 20:4, n-6)
induces in vivo and in vivo effects typical of a cannabinoid partial
agonist. We now report that the synthetic docosahexaenylethanolamide
(anandamide 22:6, n-3) shows similar activities. In addition we show
that these two anandamides, under certain experimental conditions,
antagonize the effects of delta 9-THC both in vivo and in vitro.
Thus a significant decrease in the potency of delta 9-THC-induced
inhibition of adenylate cyclase was observed in N18TG2 neuroblastoma
cells that were pretreated with low concentrations of anandamides.
At these low concentrations of anandamides had no effect when
applied alone. In vivo, Sabra or ICR mice were subjected to a tetrad
of tests, designed to detect cannabinoid-induced effects. Mice
pretreated (i.p.) with 10 mg/kg of delta 9-THC received injections
with anandamides. Only low doses (0.0001-0.1 mg/kg) of the
anandamides, which had no effects when administered alone, partially
or fully inhibited the THC-induced effects. These findings suggest
that the inhibition of delta 9-THC-induced effects by low doses of
anandamides may be due to partial agonistic effects of these
materials. It is possible that low doses of the anandamides are
capable of activating a Gs protein mediated signaling pathway, or
may cause an allosteric modulation of the cannabinoid receptor.
- Id Code
-
95155009
- Authors
- Wirguin I, Mechoulam R, Breuer A, Schezen E, Weidenfeld J, Brenner T
- Title
- Suppression of experimental autoimmune encephalomyelitis by
cannabinoids.
- Source
- Immunopharmacology
- Date
- 1994 Nov-Dec
- Issue
- 28(3)
- Pages
- 209-14
- Abstract
- The effect of delta 8-THC on experimental autoimmune
encephalomyelitis (EAE) was examined. delta 8-THC is an analogue of
delta 9-THC, the psychoactive component of marijuana. It is more
stable and less psychotropic than delta 9-THC and like the latter it
binds to the brain cannabinoid receptor. Two strains of rats were
inoculated for EAE, and delta 8-THC (40 mg/kg) was administered for
up to 21 days. delta 8-THC significantly reduced the incidence and
severity of neurological deficit in both rat strains. The beneficial
influence of delta 8-THC only occurred on oral administration and
not with parenteral injection. Serum corticosterone levels were
twofold elevated in rats with EAE chronically treated with delta
8-THC. These results suggest that suppression of EAE by cannabinoids
may be related to their effect on corticosterone secretion.
- Id Code
- 95116582
- Authors
- Mattes RD, Engelman K, Shaw LM, Elsohly MA
- Title
- Cannabinoids and appetite stimulation.
- Source
- Pharmacology, Biochemistry & Behavior
- Date
- 1994 Sep
- Issue
- 49(1)
- Pages
- 187-95
- Abstract
- Appetite stimulation by cannabinoids is highly variable. Four
within-subject design studies explored the effects of age, gender,
satiety status, route of drug administration, and dose on intake.
One study involved a single oral administration of active drug (15
mg males, 10 mg females) or placebo to an age and gender stratified
sample of 57 healthy, adult light marijuana users. Eleven subjects
received single doses by oral, sublingual, and inhaled routes in a
second study. In the third study, 10 subjects ingested a single oral
dose in fasted and fed states. A 2.5 mg dose was administered b.i.d.
for 3 days by oral and rectal suppository routes in the fourth
study. Mean daily energy intake was significantly elevated following
chronic dosing by rectal suppository, but not oral capsule, relative
to all acute dosing regimens except inhalation. Total daily energy
intake was comparable on fed and fasted days, suggesting satiety
mechanisms were not impaired by the drug. Subject age, gender,
reported "high," and plasma drug level were not significantly
associated with drug effects on food intake.
- Id Code
- 94011581
- Authors
- Tang JL, Lancz G, Specter S
- Title
- Delta-9-tetrahydrocannabinol-(THC)-mediated inhibition of macrophage
macromolecular metabolism is antagonized by human serum proteins and
by cell surface proteins.
- Source
- International Journal of Immunopharmacology
- Date
- 1993 Aug
- Issue
- 15(6)
- Pages
- 665-72
- Abstract
- Our previous study demonstrated THC-inhibited DNA synthesis and the
phagocytic activity of P388D1 cells [Tang, Lancz, Specter & Bullock
(1992) Int. J. Immunopharmac., 14, 253-262]. The ability of proteins
in human and bovine sera and of constitutive cellular proteins to
modulate the biologic activity of THC was investigated. Both human
and fetal bovine sera antagonized a THC-mediated inhibition of
P388D1 cell DNA synthesis in a dose-dependent manner. This
antagonism was proportional to the protein concentration present in
the medium. Both albumin and gamma-globulins influenced THC's
inhibitory effects, although they were less potent alpha/beta serum
lipoproteins. Exclusion of fatty acid moieties from the albumin did
not diminish its ability to antagonize THC. Tritium-labeled THC was
acid precipitable only after incubation with bovine or human serum
albumin but not DNA, suggesting a physical interaction between the
cannabinoid and the protein. Further studies showed that
pre-treating cells with trypsin to remove surface proteins
significantly enhanced the inhibitory activity of sub-toxic
concentrations of THC. Thus, the data indicate that the magnitude of
THC's biological effects is determined by the presence and
concentration of soluble proteins in the microenvironment and by
constitutive proteins present on the cell surface.
- Id Code
- 93197343
- Authors
- Mattes RD, Shaw LM, Edling-Owens J, Engelman K, Elsohly MA
- Title
- Bypassing the first-pass effect for the therapeutic use of
cannabinoids.
- Source
- Pharmacology, Biochemistry & Behavior
- Date
- 1993 Mar
- Issue
- 44(3)
- Pages
- 745-7
- Abstract
- An oral formulation of delta-9-tetrahydrocannabinol (THC) in sesame
oil (Marinol) is at present used for the management of
chemotherapy-related nausea and emesis. However, due partly to poor
bioavailability, its efficacy is variable. To circumvent possible
metabolism in the gut and a first-pass effect by the liver, a
suppository formulation of THC hemisuccinate ester was prepared.
Administration of the suppository containing 11.8 mg of the
hemisuccinate ester (equivalent to 9 mg THC) to three adult females
(two of whom had previously exhibited low plasma drug levels
following a 10-mg dose of the oral formulation) led to a marked and
sustained elevation of plasma drug levels. Areas under the curves
for plasma THC were more than 30-fold higher than after oral dosing.
The suppository was well tolerated. The higher and more sustained
plasma drug level achieved with this new formulation should enhance
its antiemetic efficacy.
- Id Code
- 92373428
- Authors
- Hollister LE
- Title
- Marijuana and immunity. [Review]
- Source
- Journal of Psychoactive Drugs
- Date
- 1992 Apr-Jun
- Issue
- 24(2)
- Pages
- 159-64
- Abstract
- Despite the fairly large literature that developed during the past
15 years or so, the effect of cannabinoids on the immune system is
still unsettled. The evidence has been contradictory and is more
supportive of some degree of immunosuppression only when one
considers in vitro studies. These have been seriously flawed by the
very high concentrations of drug used to produce immunosuppression
and by the lack of comparisons with other membrane-active drugs. The
closer that experimental studies have been to actual clinical
situations, the less compelling has been the evidence. Although the
topic was of great interest during the 1970's, as indicated by the
preponderance of the references from that period, interest has waned
during the present decade. This waning of interest suggests that
perhaps most investigators feel that this line of inquiry will not
be rewarding. The AIDS epidemic has also diverted the attention of
immunologists to the far more serious problem of the truly
devastating effects a retrovirus can have on a portion of the immune
system. The relationship between the use of social drugs and the
development of clinical manifestations of AIDS has been of some
interest, however. Persons infected with the virus but not diagnosed
as AIDS have been told to avoid the use of marijuana and/or alcohol.
This advice may be reasonable as a general health measure, but
direct evidence that heeding this warning will prevent the ultimate
damage to the immune system is totally lacking.
- References
- 41
- Authors
- - Lepore M, Liu X, Savage V, Matalon D, Gardner EL
- Title
- - Genetic differences in delta 9-tetrahydrocannabinol-induced
facilitation of brain stimulation reward as measured by a rate-
frequency curve-shift electrical brain stimulation paradigm in three
different rat strains.
- Language
- - Eng
- Date
- - 1996
- Issue
- - 0024-3205
- Source
- - Life Sci
- Pages
- - PL365-72
- Country
- - ENGLAND
- Abstract
- - Lewis, Fischer 344, and Sprague-Dawley rats were implanted with
electrodes in the medial forebrain bundle and trained to lever press
for brain stimulation reward using a rate-frequency curve-shift
electrical brain stimulation paradigm based on a series of 16 pulse
frequencies ranging from 25 to 141 Hz in descending order. Once reward
thresholds were stable, rats were given 1.0 mg/kg delta 9-
tetrahydrocannabinol (delta 9-THC), the psychoactive constituent in
marijuana and hashish, or vehicle, by intraperitoneal injection. Lewis
rats showed the most pronounced delta 9-THC-induced enhancement of
brain reward functions. Sprague-Dawley rats showed an enhancement of
brain reward functions that was approximately half that seen in Lewis
rats. Brain reward functions in Fischer 344 rats were unaffected by
delta 9-THC at the dose tested. These results are consistent with
previous work showing Lewis rats to be highly sensitive to the
rewarding properties of a variety of drugs of abuse, including opiates,
cocaine, and alcohol, while Fischer 344 rats are relatively less
sensitive. They extend such previous findings to cannabinoids, and
further suggest that genetic variations to other cannabinoid effects
may also exist.
- Research Institute
- - Department of Psychiatry, Albert Einstein College of Medicine, New
York, NY 10461-1602, USA.
- Source
- - Life Sci 1996;58(25):PL365-72
- Authors
- - Onaivi ES, Chakrabarti A, Gwebu ET, Chaudhuri G
- Title
- - Neurobehavioral effects of delta 9-THC and cannabinoid (CB1) receptor
gene expression in mice.
- Language
- - Eng
- Date
- - 1995 Dec 14
- Issue
- - 0166-4328
- Source
- - Behav Brain Res
- Pages
- - 115-25
- Country
- - NETHERLANDS
- Abstract
- - The differential sensitivity following the administration of delta 9-
THC to 3 mouse strains, C57BL/6, DBA/2 and ICR mice, indicated that
some of the neurobehavioral changes may be attributable to genetic
differences. The objective of this study was to determine the extent to
which the cannabinoid (CB1) receptor is involved in the observed
behavioral changes following delta 9-THC administration. This objective
was addressed by experiments using: (1) DNA-PCR and reverse PCR; (2)
systemic administration of delta 9-THC, and; (3) intracerebral
microinjection of delta 9-THC. The site specificity of action of delta
9-THC in the brain was determined using stereotaxic surgical
approaches. The intracerebral microinjection of delta 9-THC into the
nucleus accumbens was found to induce catalepsy, while injection of
delta 9-THC into the central nucleus of amygdala resulted in the
production of an anxiogenic-like response. Although the DNA-PCR data
indicated that the CB1 gene appeared to be identical and intronless in
all 3 mouse strains, the reverse PCR data showed two additional
distinct CB1 mRNAs in the C57BL/6 mouse which also differed in pain
sensitivity and rectal temperature changes following the administration
of delta 9-THC. It is suggested that the diverse neurobehavioral
alterations induced by delta 9-THC may not be mediated solely by the
CB1 receptors in the brain and that the CB1 genes may not be uniform in
the mouse strains.
- Research Institute
- - Department of Pharmacology, Meharry Medical College, Nashville, TN
37208, USA.
- Source
- - Behav Brain Res 1995 Dec 14;72(1-2):115-25
- Authors
- - Wallace JM, Lim R, Browdy BL, Hopewell PC, Glassroth J, Rosen MJ, Reichman LB, Kvale PA
- Title
- - Risk factors and outcomes associated with identification of Aspergillus
in respiratory specimens from persons with HIV disease. Pulmonary
Complications of HIV Infection Study Group.
- Language
- - Eng
- Date
- - 1998 Jul
- Issue
- - 0012-3692
- Source
- - Chest
- Pages
- - 131-7
- Country
- - UNITED STATES
- Abstract
- - STUDY OBJECTIVES: To examine the significance of previously suggested
risk factors and assess outcomes associated with Aspergillus
identification in respiratory specimens from HIV-seropositive
individuals. DESIGN: This was a nested case-control study. Patients who
had Aspergillus species identified in respiratory specimens were
matched at the time of study entry 1:2 with control subjects according
to study center, age, gender, race, HIV transmission category, and CD4
count. SETTING: The multicenter Pulmonary Complications of HIV
Infection Study. PARTICIPANTS: HIV-seropositive study participants.
MEASUREMENTS AND RESULTS: Between November 1988 and March 1994,
Aspergillus species were detected in respiratory specimens from 19
(1.6%) participants. The rate of Aspergillus identification among
participants with CD4 counts <200 cells per cubic millimeter during
years 2 through 5 after study entry ranged from 1.2 to 1.9%.
Neutropenia, a CD4 count <30 cells per cubic millimeter, corticosteroid
use, and Pneumocystis carinii infection were associated with subsequent
identification of Aspergillus in respiratory specimens. Cigarette and
marijuana use, previously suggested risk factors, were not associated
with Aspergillus respiratory infection. A substantially greater
proportion of patients with Aspergillus compared with control subjects
died during the study (90% vs 21%). Excluding four cases first
diagnosed at autopsy, 67% died within 60 days after Aspergillus was
detected. CONCLUSIONS: Although Aspergillus is infrequently isolated
from HIV-infected persons, the associated high mortality would support
serious consideration of its clinical significance in those with
advanced disease and risk factors.
- Research Institute
- - Department of Medicine, Olive View-UCLA Medical Center, Sylmar, Calif,
USA.
- Source
- - Chest 1998 Jul;114(1):131-7
- Authors
- - Mathew RJ, Wilson WH, Turkington TG, Coleman RE
- Title
- - Cerebellar activity and disturbed time sense after THC.
- Language
- - Eng
- Date
- - 1998 Jun 29
- Issue
- - 0006-8993
- Source
- - Brain Res
- Pages
- - 183-9
- Country
- - NETHERLANDS
- Abstract
- - Because marijuana continues to be the most commonly used illicit drug,
its effects on the brain function are of major interest. We utilized
positron emission tomography (PET) and magnetic resonance imaging (MRI)
to study the effects of delta-9-tetrahydrocannabinol (THC) infusion on
brain blood flow and its behavioral correlates in 46 volunteers.
Consistent with previous reports, there was a significant increase in
cortical and cerebellar blood flow following THC, but not all subjects
showed this effect. Those who showed a decrease in cerebellar CBF also
had a significant alteration in time sense. The relationship between
decreased cerebellar flow and impaired time sense is of interest
because the cerebellum has been linked to an internal timing system.
Copyright 1998 Elsevier Science B.V. All rights reserved.
- Research Institute
- - Department of Psychiatry and Radiology, Duke University Medical Center,
Box 3972, Durham, NC 27710, USA. mathe008@mc.duke.edu
- Source
- - Brain Res 1998 Jun 29;797(2):183-9
- Authors
- - Cabral GA, Dove Pettit DA
- Title
- - Drugs and immunity: cannabinoids and their role in decreased resistance
to infectious disease.
- Language
- - Eng
- Date
- - 1998 Mar 15
- Issue
- - 0165-5728
- Source
- - J Neuroimmunol
- Pages
- - 116-23
- Country
- - NETHERLANDS
- Abstract
- - Marijuana, Cannabis sativa, elicits a variety of effects in
experimental animals and humans. Delta-9-tetrahydrocannabinol (THC) is
the major psychoactive component in marijuana. This substance has been
shown, also, to be immunosuppressive and to decrease host resistance to
bacterial, protozoan, and viral infections. Macrophages, T lymphocytes,
and natural killer cells appear to be major targets of the
immunosuppressive effects of THC. Definitive data which directly link
marijuana use to increased susceptibility to infection in humans
currently is unavailable. However, cumulative reports indicating that
THC alters resistance to infection in vitro and in a variety of
experimental animals support the hypothesis that a similar effect
occurs in humans.
- Research Institute
- - Department of Microbiology and Immunology, Medical College of
Virginia/Virginia Commonwealth University, Richmond 23298-0678, USA.
gacabral@gems.vcu.edu
- References
- - 57
- Source
- - J Neuroimmunol 1998 Mar 15;83(1-2):116-23
- Authors
- - Kirk JM, Doty P, De Wit H
- Title
- - Effects of expectancies on subjective responses to oral delta9-
tetrahydrocannabinol.
- Language
- - Eng
- Date
- - 1998 Feb
- Issue
- - 0091-3057
- Source
- - Pharmacol Biochem Behav
- Pages
- - 287-93
- Country
- - UNITED STATES
- Abstract
- - The effects of expectancies on subjective responses to oral delta9-
tetrahydrocannabinol (delta9-THC) were examined. Thirty-five regular
marijuana users were assigned to one of two groups: one group was told
that they may receive a cannabinoid or placebo and a second group was
told that they may receive a drug from one of several classes of drugs
(e.g., stimulant, sedative, antiemetic) or placebo. Regardless of the
group to which they were assigned, subjects received each of two oral
doses of delta9-THC (7.5 and 15 mg) and placebo, one dose per session,
for a total of three sessions. Measures of subjective effects,
including visual analog scales and the Addiction Research Center
Inventory (ARCI), were administered at 0.5-h intervals throughout each
session. Consistent with previous research using other drugs, subjects
in the current experiment who expected to receive a cannabinoid
reported greater pleasurable effects than subjects who did not have
this expectancy. The results have implications for understanding the
effects of cannabinoids when used in both recreational and clinical
settings.
- Research Institute
- - Department of Psychiatry, The University of Chicago, IL 60637, USA.
- Source
- - Pharmacol Biochem Behav 1998 Feb;59(2):287-93
- Authors
- - McClure GY, McMillan DE
- Title
- - Effects of drugs on response duration differentiation. VI: differential
effects under differential reinforcement of low rates of responding
schedules.
- Language
- - Eng
- Date
- - 1997 Jun
- Issue
- - 0022-3565
- Source
- - J Pharmacol Exp Ther
- Pages
- - 1368-80
- Country
- - UNITED STATES
- Abstract
- - The effects of methamphetamine, phencyclidine and delta9-
tetrahydrocannabinol on responding under differential reinforcement of
low rate schedules (DRL schedules) were studied under three different
DRL time requirements. Under the DRL schedules studied, rats were
required to space responses at least a minimum, but not more than a
maximum, time interval apart. The time intervals between responses
(interresponse times, or IRTs), when plotted as a frequency
distribution, were usually a normal distribution with the peak at or
near the minimum IRT required for delivery of the reinforcer.
Methamphetamine flattened the IRT distribution and increased the
frequency of long pauses under the DRL 1-1.3 sec schedule, but shifted
the IRT distribution toward shorter IRTs under the DRL 4-5.2 and 10-13
sec schedules. Under the DRL 1-1.3 sec schedule, phencyclidine also
increased long pauses. Under the DRL 4-5.2 sec and 10-13 sec schedules,
phencyclidine produced dual effects on the IRT relative frequency
distributions producing increases in the proportion of short IRTs
similar to methamphetamine at low doses, but higher doses increased
long pauses as well. delta9-Tetrahydrocannabinol had little effect on
responding under the DRL 1-1.3 sec and DRL 4-5.2 sec schedules, but it
greatly increased the relative frequency of short IRTs under the DRL 10-
13 sec schedule. Thus the effects of drugs on responding under these
DRL schedules depended on the drug, the dose and the time requirements
of the schedule, which suggests that a simple description of the
effects of drugs on timing behavior or time perception is inadequate.
- Research Institute
- - Department of Pharmacology and Toxicology, University of Arkansas for
Medical Sciences, Little Rock 72205, USA.
- Source
- - J Pharmacol Exp Ther 1997 Jun;281(3):1368-80
- Authors
- - McClure GY, Wenger GR, McMillan DE
- Title
- - Effects of drugs on response duration differentiation. V: differential
effects under temporal response differentiation schedules.
- Language
- - Eng
- Date
- - 1997 Jun
- Issue
- - 0022-3565
- Source
- - J Pharmacol Exp Ther
- Pages
- - 1357-67
- Country
- - UNITED STATES
- Abstract
- - The effects of methamphetamine, phencyclidine and delta9-
tetrahydrocannabinol on responding under temporal response
differentiation schedules were studied under three different time
requirements. Under the schedules studied, Sprague-Dawley rats were
required to make a continuous response for at least a minimum time
duration, but not more than a maximum. Baseline performance under a
temporal differentiation schedule usually produces a normal frequency
distribution of response durations with the peak at or near the minimum
duration required for delivery of the reinforcer. These frequencies
were summed to calculate cumulative frequencies that were plotted as
sigmoidal curves. Under the temporal differentiation 1-1.3 sec
schedule, methamphetamine increased the frequency of short response
durations at low doses, whereas high doses produced both long and short
response durations, flattening the relative frequency distribution.
Under the temporal differentiation 4-5.2 sec and 10-13 sec schedules,
methamphetamine produced only short response durations, which shifted
the relative frequency and cumulative frequency distribution of
response durations leftward. delta9-Tetrahydrocannabinol had little
effect under the temporal differentiation 1-1.3 sec and 4-5.2 sec
schedules, but it greatly increased the relative frequency of short
response durations under the 10-13 sec schedule. Phencyclidine produced
a similar effect under all temporal differentiation schedules,
increasing the relative frequency of short response durations. Thus the
effect of drugs on timing behavior under these temporal differentiation
schedules not only depended on the drug, but also depended on the dose
and the time parameters of the schedule. These data suggest that drugs
produce multiple effects on timing behaviors that depend on complex
interactions among several factors.
- Research Institute
- - Department of Pharmacology and Toxicology, University of Arkansas for
Medical Sciences, Little Rock 72205, USA.
- Source
- - J Pharmacol Exp Ther 1997 Jun;281(3):1357-67
- Authors
- - McPartland JM, Pruitt PL
- Title
- - Medical marijuana and its use by the immunocompromised.
- Language
- - Eng
- Date
- - 1997 May
- Issue
- - 1078-6791
- Source
- - Altern Ther Health Med
- Pages
- - 39-45
- Country
- - UNITED STATES
- Abstract
- - BACKGROUND: Those immunocompromised by AIDS or cancer chemotherapy use
marijuana to allay symptoms of their disease or treatment. Some
researchers believe that marijuana may further suppress the immune
system. A list of immunological hazards that may be present in
marijuana was collated and assessed, and clinical recommendations
regarding the use of marijuana by immunocompromised individuals were
made. METHODS: Databases and other sources from 1964 to 1996 were
searched using keywords (e.g., cannabinoids, cannabis, hemp,
marijuana). This was supplemented by a manual search of bibliographies,
nonindexed books, and journals, and by consultation with experts. All
reports were analyzed for antecedent sources. Data validity was
assessed by source, identification methodology, and frequency of
independent observations. RESULTS: Substances implicated as potential
immunological hazards in marijuana include endogenous constituents
(cannabinoids, pyrolyzed gases, and particulates) and a longer list of
exogenous contaminants, both natural (fungi and their metabolites) and
synthetic (pesticides and adulterants). CONCLUSION: Burning of
marijuana creates toxins of combustion. Particulate toxins (tars) are
reduced by the use of vaporizer apparati. Gas-phase toxins are filtered
by water pipes, but water pipes also filter some tetrahydrocannabinol,
making this strategy counterproductive. Viable fungal spores in
marijuana pose the greatest hazard to immunocompromised patients,
though they can be sterilized by several methods. Pesticide residues
and other adulterants may be present in black-market marijuana, but are
absent in sources of marijuana that are approved by the Food and Drug
Administration.
- Research Institute
- - Vermont Alternative Medicine in Middlebury, USA.
- References
- - 101
- Source
- - Altern Ther Health Med 1997 May;3(3):39-45
- Authors
- - Brenneisen R, Egli A, Elsohly MA, Henn V, Spiess Y
- Title
- - The effect of orally and rectally administered delta 9-
tetrahydrocannabinol on spasticity: a pilot study with 2 patients.
- Language
- - Eng
- Date
- - 1996 Oct
- Issue
- - 0946-1965
- Source
- - Int J Clin Pharmacol Ther
- Pages
- - 446-52
- Country
- - GERMANY
- Abstract
- - Multiple doses of delta 9-tetrahydrocannabinol (THC) capsules (Marinol)
and THC hemisuccinate suppositories were administered in 24-hour
intervals to 2 patients with organically caused spasticity. After oral
doses of 10-15 mg THC, peak plasma levels from 2.1 to 16.9 ng/ml THC
and 74.5 to 244.0 ng/ml 11-nor-9-carboxy-delta 9-tetrahydrocannabinol
(THC-COOH, major THC metabolite) were measured by GC/MS within 1-8 h
and 2-8 h, respectively. After rectal doses of 2.5-5 mg THC, peak
plasma levels from 1.1 to 4.1 ng/ml THC and 6.1 to 42.0 ng/ml THC-COOH
were measured within 2-8 h and 1-8 h, respectively. The bioavailability
resulting from the oral formulation was 45-53% relative to the rectal
route of administration, due to a lower absorption and higher first-
pass metabolism. The effect of THC on spasticity, rigidity, and pain
was estimated by objective neurological tests (Ashworth scale, walking
ability) and patient self-rating protocols. Oral and rectal THC reduced
at a progressive stage of illness the spasticity, rigidity, and pain,
resulting in improved active and passive mobility. The relative
effectiveness of the oral vs. the rectal formulation was 25-50%.
Physiological and psychological parameters were used to monitor
psychotropic and somatic side-effects of THC. No differences in the
concentration ability, mood, and function of the cardiovascular system
could be observed after administration of THC.
- Research Institute
- - Institute of Pharmacy, University of Bern, Switzerland.
- Source
- - Int J Clin Pharmacol Ther 1996 Oct;34(10):446-52
- Id Code
- 95195588
- Authors
- Fendrich M, Mackesy-Amiti ME
- Title
- Inconsistencies in lifetime cocaine and marijuana use reports:
impact on prevalence and incidence.
- Source
- Addiction
- Date
- 1995 Jan
- Issue
- 90(1)
- Pages
- 111-8
- Abstract
- We evaluated inconsistencies in responses to questions about
lifetime cocaine and marijuana use asked of nearly 10,000
respondents from the United States in the National Longitudinal
Survey of Youth in 1984 and 1988. Our analyses showed that 14% of
all responses on cocaine use and 17% of all responses on marijuana
use were inconsistent in some way. The types of inconsistencies
varied according to the substance; cocaine reports yielded more
inconsistencies with regard to timing of first use, while for
marijuana most of the inconsistencies were with respect to use
disclosure. For both substances, lower level users were more likely
to be inconsistent in their reports of drug use. Alternative methods
for handling inconsistencies affected estimates of incidence and
prevalence. Inconsistencies also varied according to respondent
race/ethnicity. Implications of these findings for program
evaluation are discussed.