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.