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Marijuana components modulate a variety of immune response parameters. The cannabinoids delta 9-tetrahydrocannabinol (THC) and 11-hydroxy-tetrahydrocannabinol (11 OH-THC) are known to depress the in vitro proliferative response of murine lymphoid cells to the mitogens concanavalin A (Con A) and phytohemagglutinin (PHA). In the present report the effects of THC and 11 OH-THC on adult thymus and spleen cells were compared to effects on lymphoid cells of those organs from juvenile mice at various ages. The results demonstrate differences in susceptibility to cannabinoid-induced suppression by lymphoid cells from different organs and different age mice. In adults, thymus cells were suppressed more readily than spleen cells. Splenocytes from mice under 2 weeks old were suppressed much more readily than those from older mice. Cell populations from organs with higher proportions of L3T4+/Lyt2- cells were more difficult to suppress. The possible mechanisms involved and directions for future work are discussed.

The tetrahydrocannabinol (THC) content of more than 180 samples of fresh illicit Cannabis products, seized by H.M. Customs and Excise on entry into Great Britain and Northern Ireland over the period 1984-1989, has been determined by gas chromatography. The average THC content of herbal cannabis remained high due to good quality cannabis from Jamaica and the USA, but that of cannabis resin was slightly lower. Resin from Morocco has changed significantly in its physical appearance. There was no fresh seizure of cannabis oil in this period.

Authors investigated some fiber and some hashish hemp sorts concerning their trichomes on the leaves. Histochemical reactions were developed using the Fast Blue Salt (FBB) reagent applied so far only thin layer chromatography. Glandular hairs were found giving positive reactions due to cannabinoids contained by the cells. The electron microscopic features were studied and the cannabinoid content was measured with GC. A correlation was found between the number of typical glandular hairs and cannabinoid content.

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.

A radioimmunoassay (R.I.A.), using a sheep antiserum and 3-H-T.H.C., has been developed for the measurement of tetrahydrocannabinol (T.H.C.) in plasma and urine. The antiserum cross-reacts with T.H.C. metabolites, but nevertheless possesses sufficient group specificity and sensitivity to permit measurement of cannabinoids in plasma and urine of animals and volunteers following the administration of pure T.H.C. Subjective effects experienced by the volunteers seemed to correlate with plasma-T.H.C. levels. The examination of random plasma urine samples collected from patients attending a drug-addiction clinic revealed the presence of measurable amounts of cannabinoids in several of them.

The crystal and molecular structure of the title compound C-22H-30O-4, has been determined by X-ray methods using 1106 reflections above background level collected by counter methods. The crystals are orthorhombic, space group P2-12-12-1 with cell dimensions a equals 16.514(2) A; b equals 14.324(2) A; c equals 8.744(1) A; there are four molecules per unit cell. The structure was refined to an R of 0.084 (weighted R-w equals 0.068). The cyclohexene and the pyran part of the molecule occurs in the half-chair conformation. The bond distances and angles, and a slight twist of the benzene ring, indicate considerable stains in the aromatic system. Both the phenolic and carboxylic group are significantly out of the plane through the aromatig ring. The angle between this plane and a plane through the cyclohexene ring is 37.7 degrees. The pentyl sidechain occurs in an extended gauche conformation, and the thermal parameters of this part of the molecule are very high. The molecules are held together by van der Waals forces in the c-directions, and hydrogen bonds (2.688 A) from phenolic to carboxylic groups in the a-b plane. There is a short ultra-molecular hydrogen bond (2.490 A) from the carboxylic group to the pyran oxygen.

Changes in smoking behavior in response to a change in marijuana potency were measured in marijuana users. A marijuana cigarette containing 1.2% or 3.9% tetrahydrocannabinol (THC) was smoked on separate days by ten experienced users. Puff volume, duration and number, interpuff interval, inhalation volume and duration were averaged for each cigarette. The high potency cigarettes were smoked with more puffs and longer interpuff intervals, but also with greater inhaled volumes of air, thereby diluting the marijuana smoke.

1. The oral sedative potencies of cannabis herb, crude ethanolic and petroleum-ether fractions, were assayed against delta'-trans-tetrahydrocannabinol (THC) administered orally to mice, by measuring spontaneous motor activity over 30 min periods, at selected times, up to 6 h. 2. The THC contents of the extracts were determined chemically by gas-liquid chromatography analysis and the B/C ratio (biological activity divided by chemical activity) calculated for each. The B/C values for cannabis herb, which contained THC but no CBD, was 4.47 and for ethanolic and petroleum-ether extracts, 5.26 and 4.39, respectively. 3. The sedative potency expressed as SDA50, the dose required to give 50% effect over 6 h, was 1.06 (0.98 to 1.15) mg/kg for THC; 4.72 (4.22 to 5.27) mg/kg for cannabidiol and 1.26 (1.22 to 1.80) mg/kg for chlorpromazine. 4. An infusion of cannabis herb made with boiling water was shown to have sedative activity of very low potency. 5. When the cannabinoids were completely extracted from a sample of herb with petroleum-ether the aqueous and ethanolic extracts of the marc had some sedative activity; but the 70% ethanolic fraction had none. 6. The sedative activity of THC, cannabis herb and a water soluble fraction is blocked by aspirin, a cyclo-oxygenase inhibitor, and restored by prostaglandin E2 (PGE2). 7. The sedative effect of chlorpromazine is not blocked by aspirin.

Selection and culture in a Phytotron of plants of Cannabis sativa L. with high content of propyl-THC are obtained. Then it was possible to isolate a large quantity of propyl-THC by column chromatography. Spectroscopic analysis is done. Pharmacological tests are being run; first results revealed the allergenicity of this substance by comparison with the properties of tetrahydrocannabinol, the active principle of Cannabis.

The tetrahydrocannabinol (THC) contents of 220 samples of fresh illicit Cannabis products seized on entry into the United Kingdom of Great Britain and Northern Ireland over the period 1979-1981 have been determined by gas chromatography. During that period there was a general increase in the quality of both cannabis and cannabis resin, but with wide variations in THC contents both within and between countries. Some very high quality samples of cannabis, cannabis resin and cannabis oil from the Indian sub-continent have been analysed. There have been considerable changes in the number of fresh samples from several countries, compared with the previous survey. Fresh cannabis oil samples were very rare during the period covered by this survey.

A selective introductory review of the Cannabis literature is presented. Subjects reviewed include the relative psychoactivities of Cannabis constituents, the disposition and distribution of THC and its metabolites, the relative psychoactivities of THC metabolites, and the use of cannabinoid concentrations in physiological fluids in interpretations of the significance of Cannabis-induced effects. The pharmacology of cannabinoids in humans is emphasized.

Using a simple injection adapter of our own design, the tetrahydrocannabinol content of marlhuana was determined by gas chromatography. The injection method obviates the need for preliminary extractions and allows analyses to be conducted on milligram quantities in less than thirty minutes.

The tetrahydrocannabinol (THC) content of 304 seizures of illicit Cannabis products was determined using gas chromatography. This procedure results in the conversion of THC acid to THC itself and thus gives the total THC content of the material, which reflects its potency as experienced by the smokers. The study was carried out over three years, thus enabling comparisons to be made between THC levels from a given country of origin over this time span in addition to any variations between the countries. In the early part of the study, herbal cannabis from South East Asia was consistently the best quality and that from the Caribbean the poorest quality. In the third year of the study, the material from South East Asia was in general no richer in THC than material from other areas of the world. Cannabis resins normally had higher THC contents than most herbal material, but the highest levels were found in "hash oil" from the Middle East and the Indian subcontinent.

In a 6-year period, 435 alleged cannabis samples were accessioned by an urban street drug analysis program, and clinical histories were correlated with laboratory results. The most common reason for submission of a sample was suspicion of adulteration; however, such samples were usually unadulterated but had high potency as measured by delta 9-tetrahydrocannabinol concentration. Adverse reactions occurring in nonadulterated samples were not associated with high potencies. The validity of cannabis products distributed illicitly and analyzed was over 94%. Exotic varieties were more potent than less expensive cannabis. The absolute amount of delta 9-tetrahydrocannabinol ranged from 1.5 to 144.9 mg.

HPLC systems were developed to permit quantitative separation of delta9-tetrahydrocannabinol from many of the heptane extractable lipoidal and other endogenous substances in biological fluids. These substances interfered with the quantification by flame ionization GLC of unmodified compound and by electron capture GLC of pentafluorobenzoylated compound. Reverse phase HPLC elution, with 47% acetonitrile in water, and normal phase HPLC with 25% chloroform in heptane, separated tetrahydrocannabinol from 11-hydroxy-delta9-tetrahydrocannabinol and other monohydroxylated tetrahydrocannabinols. These systems also purified stock solutions of tetrahydrocannabinol from accompanying contaminants. The various monohydroxylated tetrahydrocannabinols were resolved from each other in normal phase, 80% chloroform in heptane. The delta8 and delta9-tetrahydrocannabinols were separable in normal phase with 5% tetrahydrofuran in hexane. The GLC analysis of pentafluorobenzoylated tetrahydrocannabinol had a sensitivity of 1 ng/ml of plasma with an estimated 5% standard error of an assay with the extraction and GLC procedures given herein. Radiochemical analysis of the HPLC separated fraction had s sensitivity of 0.2 ng/ml of plasma with an estimated 2% standard error of an assay. There was no significant difference between the liquid scintillation and electron capture GLC assays of the HPLC separated delta9-tetrahydrocannabinol obtained from the plasma of dogs administered the drug. Radiolabelled compounds can be added to plasma samples as internal standards to determine the recovery efficiencies of the several procedures in the analysis of unlabelled tetrahydrocannabinol.

Novel RIA's have been developed for marijuana detection. Modified simple techniques measure the "acute" metabolites in minute saliva, breath, and dried blood samples. Solid purified antibody matches the sensitivity and yields sensitivity values identical to liquid assays. The importance of the polar 9-substituted metabolites (9SM) of THC in acute users is shown by time course data that indicate their levels remain high in the critical post-intoxication period when delta 9-THC clears from the blood. Therefore a single-tube assay using solid-phase reagents was constructed to quantitate simultaneously delta 9-THC and 9SM. When delta 9-THC values are low or questionable in subject samples, 9SM would appear useful to confirm or refute acute marijuana use.

Plasma chromatography as a method for ultratrace qualitative and quantitative detection of organic compounds is especially well suited for detection of gas chromatographic effluents. The optimum range of sample quantity is 10-6 to 10-12 g for detection and identification of a compound by use of its characteristic positive and negative mobility spectra. The type of reference mobility spectra produced by alkanes, aromatics, esters, halogenated compounds, nitrogenated compounds and organic acids have been previously reported. This study presents the reference mobility spectra produced for lysergic acid diethylamide (LSD), delta-9-tetrahydrocannabinol (delta-9-THC), digitoxigenin and several biochemical compounds of research significance. LSD and delat-9-THC in a mixture can be detected and identified by plasma chromatography positive mobility spectra in quantities of 10-7 g or less. All the compounds investigated in this study display strong MH-+ ions along with other ions primarily of the type (M)NO-+, (M)2H-+. None of these compounds exhibits negative mobility spectra.

Cannabinoid acids readily decarboxylate to the corresponding cannabinoid. Methods are available for the determination of delta 9-tetrahydrocannabinol (THC) and its acids (THCA) and published data on the levels of these compounds in cannabis are summarized. Using gas and liquid chromatography, fresh cannabis (64 samples) and cannabis resin (26 samples) from different countries were examined. Wide variations in the relative amounts of THCA and THC in cannabis were found. For cannabis resin, a wide range of values was also found (0.5: 1 to 6.1: 1), the lower values being in resins from the Indian sub-continent and the higher values in resins from the Mediterranean area. Total THC values were in the range 1.0 - 10.6% in cannabis and 6.0 - 12.5% in cannabis resin.

Particle size and mass concentration are important determinants of site and quantity of respiratory tract deposition of aerosols. Particle concentrations and size distributions of smoke from marijuana cigarettes with different concentrations (as measured in the marijuana leaf) of delta 9-tetrahydrocannabinol (delta 9-THC) were measured using a single particle aerodynamic relaxation time (SPART) analyzer. The SPART analyzer measures aerodynamic diameter of single suspended particles at a rate of 3000/min. Cigarettes were smoked using a 35-cc, 2-sec puffing device attached to a diluter; dilution and analysis were completed within 4 sec of puff generation. The size distribution of smoke from all marijuana cigarettes was similar to that for tobacco cigarettes, ranging from 0.35 to 0.43 micron (count median aerodynamic diameter). The particle number and mass concentration increased as delta 9-THC concentration increased, being, respectively, 2.2- and 3.8-fold higher in the marijuana cigarette leaf with highest delta 9-THC concentration compared to the placebo marijuana cigarette. These data indicate the need for quantitative comparisons of other potentially toxic constituents in marijuana cigarettes of different delta 9-THC concentrations.

The THC-content in 1100 samples of cannabis resin and 600 of marihuana has been determined. The content of THC varied much, in the resin groups mostly depending on the origin and age of the resin and in the marihuana groups depending on the origin and race of the seeds.

Ten male subjects smoked placebo marijuana cigarettes spiked with delta 9-tetrahydrocannabinol (THC) at 150 micrograms/kg body weight. Plasma and urine samples were collected for 22 hr after smoking. Total cross-reacting cannabinoids were measured by immunoassay (EMIT) and THC and major metabolites were identified and quantitated by gas chromatographic/mass spectrometric (GC/MS) procedures. In plasma, THC concentration provided the best indication of recent (less than 6 hr) smoking. In enzyme-hydrolyzed urine, 8 beta, 11-dihydroxy-THC at high concentration was identified in the earliest voidings, falling rapidly to the limit of detection before 22 hr in most subjects. Levels above 15 to 20 ng/mL were indicative of use within the previous 4 to 6 hr.

Four hundred forty-nine fresh cannabis plants and 26 fruiting tops harvested in Jutland (Denmark) from July to September 1988 were characterized according to weight, height, marihuana yield, and cannabinoid content. The median weights were 308 g and 584 g for plants grown outdoors (n = 418) and in greenhouses (n = 31), respectively. The average marihuana yield was 8.7% for the plants grown outdoors and slightly lower for the greenhouse plants. Great variations, however, were seen both between and within the individual harvests. The mean concentration of total THC (tetrahydrocannabinol) was 0.87% for the plants grown outdoors. An increase according to the month of harvest was observed. For plants grown in greenhouses the mean value of total THC was 1.35%, while the mean concentration of fruiting tops was 2.13%. All plants contained cannabidiol (CBD), but only negligible concentrations of other cannabinoids. In approximately 80% of the plants the THC content was higher than the CBD content (drug type), while the rest either contained equal concentrations (intermediate type) or most CBD (fiber type).

There are many different species of cannabis plants, but their psychoactive properties mainly depend on the concentration of tetrahydrocannabinol (THC), which may vary according to genetic factors and environmental influences. On the basis of the THC content all cannabis plants are divided into fibre-type and drug-type plants. The fibre-type plant does not exceed 0.4 per cent of THC while the drug-type plant usually contains up to 5 per cent of THC, though higher percentages (up to 10 per cent) have been reported. A study of the characteristics of cannabis seeds and the influence of environmental conditions on the content of THC in cannabis plants grown in northern, southern and insular Italy has shown that the fibre-type plants contain mean values of THC in a range from 0.058 to 0.299 per cent. The content of THC in the drug-type plants grown in Sicily and Tuscany ranged from 0.82 to 1.31 per cent +/- 0.49 per cent. In 1984, the Commission of the European Communities prepared a regulation to prevent diffusion of the drug-type cannabis, providing that raw material could not be imported if its THC content exceeded 0.5 per cent from 1984 to 1987 and after that period the maximum limit would be set up to 0.3 per cent.

The butyl homologues of delta1-tetrahydrocannabinol, delta1-tetrahydrocannabinolic acid, cannabinol and cannabidiol have been identified in several samples of cannabis. 8 samples contained delta1-tetrahydrocannabinolic acid, one sample contained cannabinol and one sample contained both cannabinol and cannabidiol. Separation by gas chromatography and identification by gas chromotography-mass spectrometry was achieved by the preparation of trimethylsilyl, d9-trimethylsilyl, triethylsilyl and tri-n-propylsilyl derivatives.

1 Conditions have been worked out for a reliable estimation of the cataleptic activity of delta'-trans-tetrahydrocannabinol (THC) after oral administration to mice, using the ring test over a period of 6 h. 2 By this method, the activity of cannabis herb and 5 crude fractions were measured against THC; at the same time the THC contents were determined chemically. 3 The B/C ratio (biological activity divided by chemical assay) was calculated for each. With cannabis herb the value was 3.3 and with extracts prepared with ethanol or 70% ethanol the values ranged from 3.2 to 7.1, indicating that in all samples the activity was much higher than would be expected from their THC content. 4. The cannabinoids were completely extracted from a sample of herb using petroleum spirit and the marc examined for a possible synergist. Surprisingly, it contained a powerful inhibitor of the action of THC, which could be restored by intraperitoneal prostaglandin E2 (3 microgram/kg). Some crude fractions had inhibitory activities about 10 times that of aspirin. 5 In contrast, the petroleum spirit extract (referred to in 4) had a surprisingly high B/C ratio of 23, indicating that a powerful synergist of THC activity is present. 6 The net effect of the herb and ethanol extracts is probably due to a balance of synergist and inhibitor.