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ABEL EL; SUBRAMANIAN MG
Effects of low doses of alcohol on delta-9-tetrahydrocannabinol's effects in pregnant rats.
Life Sci. 1990; 47(18): 1677-82
Pregnant rats were intubated with 50 mg/kg of delta-9-tetrahydrocannabinol (THC) or with THC plus alcohol to determine if a low dose of alcohol (1 g/kg) would significantly increase blood levels of THC. On the basis of this study, a second study was conducted in which pregnant rats were intubated with THC (50, 25 or 0 mg/kg) plus alcohol (2, 1 or 0 g/kg) from gestation day six to parturition. THC reduced birth weights but did not significantly affect litter size or passive avoidance learning. Alcohol did not have a significant effect on offspring birth weight nor did it interact with THC to affect offspring.

ADLAF, EDWARD M; SMART, REGINALD G
Drug Use and Religious Affiliation, Feelings and Behavior
British Journal of Addiction; 1985, 80, 2, June, 163-171.
Examined is the relationship between drug use & religious affiliation, intensity of religious feelings, & frequency of church attendance in a sample of Ontario adolescents (number of cases = 2,066). Six drug-use measures were employed: alcohol use, cannabis use, nonmedical & medical drug use, hallucinogen use, & polydrug use. The findings indicate that religious affiliation was insignificantly related to drug use. The only exception was for alcohol use, in which case nonaffiliated respondents used less frequently than did Protestants or Roman Catholics. Church attendance exhibited a stronger negative effect on drug use than did religiosity; however, the effect of the latter had greater impact among females than among males. Overall, the impact of both variables increased as the drug examined moved toward the upper end of the licit-illicit continuum. Many of the results varied according to students' gender & age.

Aldrich, Michael R.
Tantric Cannabis Use in India.
J. Psychedelic Drugs 9(3):227-233. (1977)

ALDRICH, MICHAEL R
Tantric cannabis use in India.
Journal of Psychedelic Drugs; 1977 Jul-Sep Vol 9(3) 227-233
The sacred beverage described in the Veda texts was probably made from a hallucinogenic mushroom, but it was replaced by hallucinogenic hemp in the 7th-11th centuries. Oral ingestion of marihuana and sexual intercourse were ritualized into a ceremony of great liberation.

ALLEYNE BC; STUART P; COPES R
Alcohol and other drug use in occupational fatalities.
J Occup Med. 1991 Apr; 33(4): 496-500
High costs and the potential risk to public health of drug-related workplace accidents are major concerns. Studies conducted to evaluate this problem are restricted by concerns for individual rights and fears of jeopardizing labor relations. However, in collaboration with the Medical Examiner's office. Alberta Occupational Health and Safety examined a unique set of data on 459 deaths occurring at work. The only illicit drug found was cannabis for which 10 workers tested positive. Forty workers tested positive for alcohol, 28 for prescription, and 22 for nonprescription drugs. Evidence of alcohol use was found in a higher percentage of fatalities due to motor vehicle accidents, falls, and being caught in or under equipment than in other types of workplace fatalities.

ALLISON KR; DIGNAM C
Social and school factors in predicting cannabis use among Ontario high school students.
Can J Public Health. 1990 Jul Aug; 81(4): 301-6
This paper explores the influence of social factors and school factors on cannabis use among Ontario high school students. The data are derived from a survey of students conducted by the Addiction Research Foundation in 1987. Multiple classification analysis was used to examine the relationship between the two groups of factors and cannabis use. Results of the analysis indicate that social factors are more highly predictive of cannabis use than are school factors. A theoretical framework specifying the influence of social and school factors on cannabis use needs to be developed and tested in order to understand this relationship more clearly.

ALTMAN, JACK L; APPEL, JAMES B; MCGOWAN, WILLIAM T
Drugs and the discrimination of duration.
Psychopharmacology; 1979 Vol 60(2) 183-188
Analyzed the effects of LSD, dextroamphetamine (DAM), chlorpromazine (CPZ), and delta-9-tetrahydrocannabinol (THC) on timing behavior with a 2-choice, discrete trial procedure in which 4 male White Carneaux pigeons were trained to discriminate visual stimuli that differed with respect to duration (long vs short--5.5 or 4.5 sec, respectively). LSD (0.01, 0.04, or 0.16 mg/kg) decreased response speed (increased latency). DAM (1.0, 2.0, or 4.0 mg/kg) increased perseveration of 'spatial bias' and, at a dose of 4.0 mg/kg, lowered response speed. CPZ (7.5, 15.0, or 30.0 mg/kg) significantly decreased accuracy and, at a dose of 30.0 mg/kg, significantly lowered speed. THC also decreased accuracy and lowered speed.

ALTMAN, JACK L
Drugs and the production of temporal intervals in the rat.
Progress in Neuro Psychopharmacology; 1977 Vol 1(3-4) 301-308
The widespread use and abuse of psychoactive compounds have increased the reports of drug-induced perceptual distortions and have generated an interest in the occurrence of such phenomena in nonhuman species. In a paradigm similar to human timing procedures, 7 male water-deprived Sprague-Dawley albino rats were differentially reinforced for depressing a lever for 4.5-5.5 sec. Administration of amphetamine and tetrahydrocannabinol resulted in a premature release of the lever ('short' errors); LSD and chlorpromazine prolonged depression of the lever beyond the required interval ('long' errors). The procedure employed appears sensitive to drug-induced shifts in timing behavior and permits direct comparison between the results of timing experiments with lower animals and the data obtained from the temporal production experiments commonly used with humans.

ALTMAN, JACK L
Drugs and the production of temporal intervals in the rat.
Progress in Neuro Psychopharmacology; 1977 Vol 1(3-4) 301-308
The widespread use and abuse of psychoactive compounds have increased the reports of drug-induced perceptual distortions and have generated an interest in the occurrence of such phenomena in nonhuman species. In a paradigm similar to human timing procedures, 7 male water-deprived Sprague-Dawley albino rats were differentially reinforced for depressing a lever for 4.5-5.5 sec. Administration of amphetamine and tetrahydrocannabinol resulted in a premature release of the lever ('short' errors); LSD and chlorpromazine prolonged depression of the lever beyond the required interval ('long' errors). The procedure employed appears sensitive to drug-induced shifts in timing behavior and permits direct comparison between the results of timing experiments with lower animals and the data obtained from the temporal production experiments commonly used with humans.

ALVES, C NORBERTO; GOYOS, A CELSO; CARLINI, E A
Aggressiveness induced by marihuana and other psychotropic drugs in REM sleep deprived rats.
Pharmacology, Biochemistry, and Behavior; 1973 Mar Vol. 1(2) 183-189
In 96 hrs, REM sleep-deprived rats were given 5-40 mg/kg of D9-tetrahydrocannabinol and several alcoholic extracts of marihuana. Aggressiveness appeared after the 1st application of the drugs and was observable for at least 4 hrs following the injection. Ss also developed a high degree of irritability. LSD-25 (.02-.08 mg/kg), mescaline (80 mg/kg), dextroamphetamine (1-4 mg/kg) and ethanol (0.8-1.6 g/kg) failed to elicit either aggressiveness or irritability in the REM sleep-deprived Ss. However, 8 and 16 mg/kg of dextroamphetamine induced aggressiveness which was, however, far below that observed in the marihuana treated Ss. Data support previous findings that the acute effects of marihuana can be dramatically changed from depression, as observed in normal Ss, to irritability and aggressiveness as observed in stressed Ss.

ANDERSON G; SCOTT M
Determination of product shelf life and activation energy for five drugs of abuse [see comments]
Clin Chem. 1991 Mar; 37(3): 398-402
Estimating the shelf life of reagents and controls is a critical step in evaluating new formulations. We describe several stability assessment techniques, giving particular attention to experimental design. Activation energy was experimentally determined for five major drugs of abuse and metabolites: morphine, 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid, amphetamine, phencyclidine, and benzoylecgonine. The use of activation energy in establishing shelf life is illustrated for SENTRY (Hycor Biomedical Inc.) Drugs of Abuse Screen Control, a liquid urine-based product.

ASUNI T; PELA OA
Drug abuse in Africa.
Bull Narc. 1986 Jan-Jun. 38(1-2). P 55-64.
Apart from cannabis abuse in northern and southern Africa and khat chewing in north-eastern Africa, the history of drug abuse in Africa is relatively short. The abuse of drugs in Africa is nevertheless escalating rapidly from cannabis abuse to the more dangerous drugs and from limited groups of drug users to a wider range of people abusing drugs. The most common and available drug of abuse is still cannabis, which is known to be a contributing factor to the occurrence of a schizophrenic-like psychosis. The trafficking in and abuse of cocaine determine the real magnitude and characteristics of the problem and to monitor its trends. A lack of funds and a shortage of adequately trained personnel have made it difficult to implement drug abuse control programmes. In addition to formal drug control involving the implementation of legislation, there is an informal system of drug abuse control operating through the family, church, school, neighbourhood and work environment, as well as healthy recreational activities. It is suggested that efforts in African countries should be directed towards strengthening not only the formal drug control system but also informal control in order to compensate for the insufficient funds and the shortage of personnel trained in implementing formal drug control measures. It is very likely that the drug problems in African countries will worsen in future unless more effective measures are implemented to arrest the current situation.

AUDETTE CA; BURSTEIN S
Inhibition of leukocyte adhesion by the in vivo and in vitro administration of cannabinoids.
Life Sci. 1990; 47(9): 753-9
Cannabinoids have been shown to affect various aspects of arachidonic acid metabolism both in vivo and in vitro. Eicosanoid metabolites of arachidonate and related octadecanoate are believed to be involved in cell adhesion processes as agonists in some instances and as antagonists in other cases. This report shows data in which cannabinoids exhibit marked inhibitory effects on the adhesion of mouse peritoneal cells to polystyrene culture dishes. The effects could be seen by in vivo administration of the drugs as well as by direct exposure of the cells in vitro. The data suggest that this inhibition of adhesion is mediated by one or more products generated by stimulation of a lipoxygenase pathway.

BARKER, MAURICE
(The nonmedical use of drugs.)
Vie medicale au Canada francaise; 1975 Apr Vol 4(4) 385-388
Based on records of hospitalized adolescents and a review of recent reports, trends in the nonmedical use of tetrahydrocannabinols, hallucinogens, amphetamines, and hypnotics are reported for the Montreal area during 1974. Marihuana continued to be a popular drug, with usage expanding to segments of the population other than 'hippies.' The most common hallucinogen used was phenylcyclohexyl-piperidine (PCP), and opiates were becoming easier to obtain. Amphetamine use was largely confined to individuals with other psychological and physical problems, and alcohol use was prevalent among young people. The properties of PCP are discussed, and a few suggestions for treating drug-using adolescents are presented.

BEARDSLEY TM
Cannabis comprehended. The 'assassin of youth' points to a new pharmacology [news]
Sci Am. 1990 Oct; 263(4): 38
[NO ABSTRACT] cannabinoid receptors

BOGGAN, WILLIAM O
Psychoactive compounds and audiogenic seizure susceptibility.
Life Sciences; 1973 Jul Vol. 13(2) 151-159
Compared the effects of several psychoactive compounds on experimental convulsions, a phenomenon that has been used as an index of CNS excitability. In experiments with C57B6, C57BL/6, C57BL/6-S, and DBA/2 mice, intraperitoneally administered LSD, mescaline, dextro- and levoamphetamine, cocaine, and morphine were all effective in blocking audiogenic seizure susceptibility. None of the compounds were effective in blocking the priming of the nonsusceptible DBA/2 Ss. This latter finding differentiates these compounds from D9-tetrahydrocannabinol which has been previously reported to block priming.

BOGUSZ M
Anmerkungen zu: 'Tetrahydrocannabinole im Haar von Haschischrauchern' S.Balabanova et al. und zu der Antwort Dr. Balabanova auf die Bemerkungen von H. Kaferstein und G. Sticht. [Comments on: 'Tetrahydrocannabinols in hair of hashish smokers', S. Balabanova
Z Rechtsmed. 1990; 103(8): 621-2
[NO ABSTRACT] THC and hair analysis

BOURDON R; GALLIOT M; DANG VU B; SANDOUK P
Exploration analytique des toxicomanies. [Analytical exploration of drug addiction]
Presse Med. 1991 Jan 26; 20(3): 124-7
The natural and synthetic substances most frequently leading to drug addiction are described. They include cannabis, opium and cocaine with their respective derivatives. The authors insist on the problems encountered by analytical chemists when they examine urine samples containing these substances, owing to their metabolic degradation and to interferences between lawful and unlawful drugs. The limitations imposed by these problems to an unambiguous interpretation of the results obtained are defined, but they do not throw any doubt on the value of these investigations.

BOYD, EUGENE S; BOYD, ELEANOR H; BROWN, LAWRENCE C
The effects of some drugs on an evoked response sensitive to tetrahydrocannabinols.
Journal of Pharmacology and Experimental Therapeutics; 1974 Jun Vol 189(3) 748-758
Compared the effects of several drugs with those of Delta-9-tetrahydrocannabinol (THC) on responses evoked in frontal lobe polysensory areas, ipsi- and contralateral to the stimulus site in primary somatosensory cortex, in squirrel monkeys with postmesencephalic or high spinal sections. THC augmented both the early evoked response and the late evoked response, which occurred 150-200 msec after the stimulus, and augmented or induced repetitive synchronous activity after the late response. Pentobarbital, ethanol, and diethyl ether depressed both early and late responses, while chlorpromazine and chloralose depressed late responses without consistently affecting early responses. Mescaline had effects similar to those of THC on late responses, but its effect on early responses was much less. LSD had little effect on early responses but depressed late responses at high doses. Phencyclidine also had little effect on early responses; it facilitated late responses at low doses and depressed them at high doses. Picrotoxin and pentylenetetrazol had effects similar to, but greater than, those of THC. Strychnine had variable, and mostly small, effects on evoked responses. Gallamine, atropine, amphetamine, levarterenol, and methoxamine were without effect.

BRON, BERNHARD
Motivation and effect of phantastica-consumption.
Praxis der Kinderpsychologie und Kinderpsychiatrie; 1976 May-Jun Vol 25(4) 128-139
Investigated the theory that drug abuse is frequently an auto-therapeutic attempt, a resistance against unbearable wishes, and an attempt to restore an unstable ego. 66 juvenile cannabis- and LSD users were examined in terms of their motivations and the effect of drug abuse. Various psychodynamic and social factors of drug abuse were found, and there was a striking correlation between specific motivations and psychopathology following drug abuse. The improvement of interpsychic conflicts and tensions expected from drug consumption were reversed in almost all cases. For example, phase specific conflicts and crisis situations were aggravated by drug use, and negative personality traits became more distinct.

BRONNER W; NYMAN P; VON MINDEN D
Detectability of phencyclidine and 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid in adulterated urine by radioimmunoassay and fluorescence polarization immunoassay.
J Anal Toxicol. 1990 Nov Dec; 14(6): 368-71
The ability to alter immunoassay test results by the addition of some commonly available chemicals to drug-positive and drug-negative urine specimens was investigated. Urine specimens containing either phencyclidine (PCP) or 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (9-THC-COOH) were adulterated with sodium chloride, bleach, vinegar, potassium hydroxide, liquid soap, 2-propanol, and ammonia. Subsequent analyses by radioimmunoassay (RIA) and fluorescence polarization immunoassay (FPIA) demonstrated false positive and false negative results with some adulterants. Radioimmunoassay false positives occurred with potassium hydroxide (PCP and THC-COOH assays) and bleach (THC-COOH assay) adulterants. Bleach (PCP assay) and soap (THC-COOH assay) additives resulted in false negative analyses by RIA. No adulterant caused FPIA false positives. FPIA false negatives occurred with bleach (PCP and THC-COOH assays) and potassium hydroxide (PCP assay) adulterants.

BROWN NK; HARVEY DJ
In vitro metabolism of cannabinol in rat, mouse, rabbit, guinea pig, hamster, gerbil and cat.
Eur J Drug Metab Pharmacokinet. 1990 Jul Sep; 15(3): 253-8
Metabolism of cannabinol (CBN) was studied in hepatic microsomal incubates from mouse, rat, rabbit, guinea pig, cat, hamster and gerbil. Metabolites were extracted with ethyl acetate, concentrated by chromatography on Sephadex LH-20 and identified by GC/MS as TMS derivatives. Six monohydroxy metabolites were identified. These had hydroxy groups at C-11 and at all positions of the pentyl side-chain. Metabolism varied considerably between the species. 11-Hydroxylation was the most prominent route in the majority of species, but in the hamster and cat the major metabolic pathway was 4'-hydroxylation. Metabolites hydroxylated in the pentyl chain were generally more abundant in guinea pig, hamster and cat.

BURSTEIN SH; AUDETTE CA; CHARALAMBOUS A; DOYLE SA; GUO Y; HUNTER SA; MAKRIYANNIS
Detection of cannabinoid receptors by photoaffinity labelling.
Biochem Biophys Res Commun. 1991 Apr 15; 176(1): 492-7
A novel [125I]-labelled photoaffinity ligand designed to detect cannabinoid binding sites has been used in mouse brain preparations and in cultured S49 mouse lymphoma cells. The ligand, 2-iodo-5'-azido-delta 8-THC, shows a high affinity for sites in both brain (Kd = 5.60 pM) and whole cell (Kd = 9.38 pM) systems. Photolabelling studies with brain samples revealed the existence of four ligand-protein adducts, of estimated molecular weights 85.5, 62.1, 30.0 and 25.5 kDa, that were diminished by prior exposure to 8 microM THC. A similar study with S49 cells gave adducts with apparent molecular weights of 62.1, 34.4, 16.9 and 13.5 kDa. The ligand produces a typical cannabinoid cataleptic response in mice suggesting that possibly one or more of the binding sites may be involved in some of the receptor mediated actions of THC.

CHEN J; PAREDES W; LOWINSON JH; GARDNER EL
Delta 9-tetrahydrocannabinol enhances presynaptic dopamine efflux in medial prefrontal cortex.
Eur J Pharmacol. 1990 Nov 6; 190(1-2): 259-62
Acute administration of 1.0-2.0 mg/kg delta 9-tetrahydrocannabinol (delta 9-THC) increased presynaptic dopamine (DA) efflux in the medial prefrontal cortex of rats, as measured by intracerebral microdialysis in awake, behaving rats. These data are congruent with suggestions that (1) marijuana's euphorigenic effects and abuse potential may be related to augmentation of presynaptic DA mechanisms, and (2) the medial prefrontal cortex may be an important site of action for drugs of abuse in general and for delta 9-THC in particular.

CHEN JP; PAREDES W; LI J; SMITH D; LOWINSON J; GARDNER EL
Delta 9-tetrahydrocannabinol produces naloxone-blockable enhancement of presynaptic basal dopamine efflux in nucleus accumbens of conscious, freely-moving rats as measured by intracerebral microdialysis.
Psychopharmacology Berl. 1990; 102(2): 156-62
This study examined the effects of acute administration of delta-9-tetrahydrocannabinol (delta 9-THC), the psychoactive ingredient in marijuana, on extracellular efflux of dopamine (DA) and its metabolites as measured by in vivo microdialysis in nucleus accumbens of conscious, freely-moving rats. delta 9-THC, at low doses (0.5-1.0 mg/kg), which significantly enhance brain stimulation reward (intracranial self-stimulation), significantly increased DA efflux in nucleus accumbens. Augmentation of DA efflux by delta 9-THC was abolished by removal of calcium (Ca++) ions from the perfusion fluid, indicating a Ca(++)-dependence of delta 9-THC's action. Augmentation of DA efflux by delta 9-THC was either totally blocked or significantly attenuated by doses of naloxone as low as 0.1 mg/kg. Given the postulated role of mesocorticolimbic DA circuits in mediating and/or modulating brain stimulation reward, the present data raise the possibility that marijuana's rewarding effects, and hence its euphorigenic effects and abuse potential, may be related to pharmacological augmentation of presynaptic DA mechanisms. Additionally, the DA mechanisms enhanced by marijuana appear to be modulated by an endogenous opioid peptide system.

CIMBURA G; LUCAS DM; BENNETT RC; DONELSON AC
Incidence and toxicological aspects of cannabis and ethanol detected in 1394 fatally injured drivers and pedestrians in Ontario (1982-1984).
J Forensic Sci. 1990 Sep; 35(5): 1035-41
A comprehensive epidemiological study of the involvement of cannabis and ethanol in motor vehicle fatalities in the Province of Ontario, Canada, is described. The study is based on toxicological analyses of blood and, when available, urine specimens. Ethanol was determined by headspace gas chromatography (GC). For cannabis, the methods employed were radioimmunoassays (RIAs) for screening and gas chromatography/mass spectrometry (GC/MS) for the determination of delta-9-tetrahydrocannabinol (THC) in blood. The study sample consisted of 1169 drivers and 225 pedestrians. THC was detected in the blood of 127 driver victims (10.9%) in concentrations ranging from 0.2 to 37 ng/mL, with a mean of 3.1 +/- 5.0 ng/mL. Ethanol was found in 667 driver victims (57.1%), in concentrations ranging from 9 to 441 mg/100 mL, with a mean of 165.8 +/- 79.5 mg/100 mL. For pedestrians, the incidence of THC and ethanol in the blood was 7.6 and 53.3%, respectively. The incidence of THC in the driver victims in this study constitutes an approximately threefold increase over the results of an Ontario study completed in 1979. At least a part of the increase may be attributed to interstudy differences in analytical methodology for cannabinoids.

COLASANTI BK
A comparison of the ocular and central effects of delta 9-tetrahydrocannabinol and cannabigerol.
J Ocul Pharmacol. 1990 Winter; 6(4): 259-69
Both delta 9-tetrahydrocannabinol (delta 9-THC) and cannabigerol, two naturally occurring marihuana cannabinoids, produced only a modest fall in intraocular pressure after acute topical application to the eyes of cats. After chronic administration unilaterally to the cornea via Alzet osmotic minipumps and connecting extraocular cannulas, however, a considerable fall in ocular tension amounting to 4 to 7 mm Hg occurred. After systemic administration of delta 9-THC to rats, polyspike discharges appeared in the cortical electroencephalogram initially during wakefulness and behavioral depression. These polyspikes subsequently became evident within rapid eye movement sleep episodes. Cannabigerol was devoid of this effect. After removal of either sympathetic or parasympathetic input to the eyes of cats, the intraocular pressure lowering effect of delta 9-THC was not changed. Neither delta 9-THC nor cannabigerol altered the rate of formation of aqueous humor. On the other hand, both cannabinoids produced a two-to three-fold increase in aqueous outflow facility. These results suggest that cannabigerol and related cannabinoids may have therapeutic potential for the treatment of glaucoma.

DARLING MR; ARENDORF TM; COLDREY NA
Effect of cannabis use on oral candidal carriage.
J Oral Pathol Med. 1990 Aug; 19(7): 319-21
The effects of cigarette smoking on oral candidal carriage and candidosis have been well documented but few similar studies on cannabis smoking have appeared, therefore it was felt that such a study needed to be undertaken. In this investigation, the effect of cannabis smoking combined with methaqualone and tobacco on candidal prevalence, density and candidosis was examined in 55 users. Age and sex matched tobacco-smoking (n = 58) and non-smoking controls (n = 50) were examined similarly. The imprint culture technique was used for harvesting Candida. Results showed an increased prevalence and density of C. albicans in cannabis users while there was no apparent difference in the prevalence of candidiasis. However, two subjects presented with oral multifocal candidiasis.

DE MELLO, A CESARIO,; ET AL
Behavioral observations on compounds found in nutmeg.
Psychopharmacologia; 1973 Vol. 31(4) 349-363
Found that myristicin and elemicin impaired the rope climbing and barpressing performance of male and female Wistar rats and caused catatonia and decreased motor activity in mice. As measured in rope climbing performance, rats developed tolerance to both myristicin and elemicin. There was cross-tolerance between myristicin and elemicin; neither showed cross-tolerance with either D9-tetrahydrocannabinol or mescaline. The activity of myristicin and elemicin and the inactivity of other nugmeg compounds (safrole, eugenol, isoeugenol, and methylisoeugenol) were not reflected in the energies of the highest occupied molecular orbital. These quantum chemical calculations also imply that the nutmeg compounds are not especially good electron donors.

DEAHL M
Cannabis and memory loss [editorial]
Br J Addict. 1991 Mar; 86(3): 249-52
[NO ABSTRACT] cannabis

DEVANE WA; HANUS L; BREUER A; PERTWEE RG; STEVENSON LA; GRIFFIN G; GIBSON D; MAN
Isolation and Structure of a Brain Constitutent That Binds to the Cannabinoid Receptor
Science 258:1946 18-DEC-92 1992
Arachydonylethanolamide, an arachidonic acid derivative in porcine brain, was identified in a screen for endogenous ligands for the cannabinoid receptor. The structure of this compound, which has been named 'anandamide,'was determined by mass spectrometry and nuclear magnetic resonance spectroscopy and was confirmed by synthesis. Anandamide inhibited the specific binding of a radiolabled cannabinoid probe to synaptosomal membranes in a manner typical of competitive ligands and produced a concentration-dependent inhibition of the electrically evoked twitch response of the mouse vas differens, a characteristic effect of psychotropic cannabinoids. These properties suggest that anandamide may function as a natural ligand for the cannabinoid receptor.

DITTRICH, A; BICKEL, P; SCHOPF, J; ZIMMER, D
(Comparisons of altered states of consciousness induced in the hallucinogens (-)-Delta9-trans-tetrahydrocannabinol (D9-THC) and N,N-dimethyltryptamine (DMT).)
Archiv fur Psychiatrie und Nervenkrankheiten; 1976 Vol 223(1) 77-87
Compared altered states of consciousness induced by the hallucinogens (-)Delta9-trans-tetrahydrocannabinol (Delta9-THC) and N,N-dimethyltryptamine (DMT) using 2 placebo control groups. 24 Ss received 250 mug Delta9 THC/kg body weight, orally, and 26 Ss were treated with 250 mug DMT im/kg. Placebo was given to 24 Ss. The effects were assessed by a questionnaire administered following the experimental conditions. Questionnaire items were combined into the following 8 scales according to their content and several criteria of the theory of mental testing: visual hallucinations (illusions), auditory hallucinations (illusions), impairment of memory and attention, depersonalization syndrome, derealization syndrome, changes of body image, euphoric state, and anxious-depressive state. The 2 hallucinogen groups differed significantly from placebo on all 8 scales. No difference, however, between Delta9-THC and DMT was significant. On the scale 'optical hallucinations (illusions),' there was evidence suggesting that DMT may have stronger effects than Delta9-THC. Methodological problems of comparing different hallucinogens are discussed.

DITTRICH, A; VON ARX, S; STAUB, S
Concerning the question of increased readiness to consume hallucinogens subsequent to experiments with hallucinogens.
Psychologie Schweizerische Zeitschrift fur Psychologie und ihre Anwendungen; 1980 Vol 39(3) 221-236
Investigated whether normal volunteers in experiments with hallucinogenic drugs would later show an increased readiness to use hallucinogens. 110 Ss who had received in 1 of 4 experiments either a hallucinogen (delta-9-tetrahydrocannabinol, N,N-dimethyltryptamine, or psilocybin) or placebo were sent a questionnaire 3-5 yrs later. 82% of the Ss responded. Analyses of data comparing the hallucinogen groups with those receiving placebo indicated that the dangers of controlled hallucinogen experiments as assessed in this study appear to be minimal. (French abstract)

DIXON L; HAAS G; WEIDEN PJ; SWEENEY J; FRANCES AJ
Drug abuse in schizophrenic patients: clinical correlates and reasons for use.
Am J Psychiatry. 1991 Feb; 148(2): 224-30
OBJECTIVE: This study aimed to 1) determine substance abuse prevalence and preference in a diverse sample of schizophrenic, schizoaffective, and schizophreniform inpatients, 2) compare drug-abusing and non-drug-abusing patients on demographic and clinical variables during the acute and stabilization phases of their hospital course, and 3) obtain data from patients on reasons for drug abuse and on acute state-related changes during periods of intoxication. METHOD: Eighty-three psychotic inpatients consecutively admitted to a New York City teaching hospital were evaluated. Sixty-eight had schizophrenia, 12 had schizoaffective disorder, and three had schizophreniform disorder diagnosed according to the Structured Clinical Interview for DSM-III-R. Each patient received ratings on the Brief Psychiatric Rating Scale, the Global Assessment Scale, and the Scale for the Assessment of Negative Symptoms at admission and at discharge, an evaluation of premorbid adjustment, and an extensive interview on drug and alcohol use. RESULTS: Forty (48%) of the patients received diagnoses of drug or alcohol abuse or dependence. The drug-abusing patients primarily used cannabis (N = 26), alcohol (N = 21), and cocaine (N = 14) and reported that they abused drugs to get 'high,' to relieve depression, and to relax. They had significantly fewer positive and negative symptoms at discharge, better sexual adjustment and worse school performance during adolescence, and more family histories of drug abuse than the non-drug-abusing patients. CONCLUSIONS: Schizophrenic patients who abuse drugs may represent a subgroup of patients with better prognoses and less severe clinical characteristics of schizophrenia, but their drug abuse may adversely affect global outcome.

DREW, W G; MILLER, LOREN L; BAUGH, E L
Effects of D9-THC, LSD-25 and scopolamine on continuous, spontaneous alternation in the -maze.
Psychopharmacologia; 1973 Vol. 32(2) 171-182
Determined the effects of D9-tetrahydrocannabinol (D9-THC), LSD-25, and scopolamine on continuous, spontaneous alternation of 56 naive, male hooded rats in the maze. LSD and scopolamine decreased the number of arm entries (responsivity) while concomitantly reducing percent alternation. D9-THC, however, reduced responsivity and percent alternation more at the lower dose (1 mg/kg) when compared to control than at the higher dose (3 mg/kg). Only scopolamine induced a significant increase in stimulus perseveration. Results are discussed in relation to the advantages afforded by the continuous spontaneous alternation procedure.

DU TOIT, BRIAN M
Historical and cultural factors influencing cannabis use among Indians in South Africa.
Journal of Psychedelic Drugs; 1977 Jul-Sep Vol 9(3) 235-246
British settlers in South Africa imported laborers from India in the period between 1855 and 1911 and prohibited their traditional use of cannabis in 1870. However, current surveys indicate that cannabis is widely used in South Africa not only by Indian and Coloured races but also by African and White races.

DUNFORD, MARTIN; HOLLAND, JACK
Coffee Shops and Tea Rooms
THE REAL GUIDE - AMSTERDAM (The Guide for the '90s; Prentice Hall Travel
COFFEE SHOPS AND TEA ROOMS: As with bars, there are two types of Amsterdam coffee shops: those whose principal business is the buying, selling, and consuming of dope, and the more traditional places that sell neither dope nor alcohol but do serve sandwiches or a light menu for lower prices than you'd pay in a full-fledged restaurant; some offer pastries or chocolates. The so-called 'smoking' coffee shops are easy to identify: brightly lit, with starkly modern furniture and an accent on healthy food, they're about as far from the cozy Dutch 'brown cafe' as it's possible to get. Smoking dope is the primary pastime (all sell a range of hash and grass), and most also have video (loud) music, and a selection of games from baccarat to pool; they're open roughly from late morning/midday until around midnight. They are currently booming, and the major Amsterdam chains - The Bulldog, Prix d'Ami, Fancy Free - seem to be opening new branches all the time: they may be identified by a cannabis-leaf sign and a slogan claiming that they serve the best quality goods on the Amsterdam dope scene. For real dope heads there's the Hash Info Museum (p93) which survives despite crackdowns. For more on dope see p.12.

DUNFORD, MARTIN; HOLLAND, JACK
Police Trouble, and a Note on Drugs. (2)
THE REAL GUIDE - AMSTERDAM (The Guide for the '90s; Prentice Hall Travel
DRUGS: Some residents claim that the liberal municipal attitude toward the sale of drugs has attracted all sorts of undesirables to the city. This is partly true, but the 'cleaning up' of the Zeedijk, once Amsterdam's heroin-dealing quarter, seems to have made open trafficking less frequent and the city a safer place. Amsterdam has sanctioned the sale of cannabis at the Melkweg and Paradiso nightspots, and at many coffee shops, since the 1960's. It's also acceptible to smoke in some bars, but since many are strongly against it, don't make any automatic assumptions. If in doubt, ask the barperson. Purchasing, transporting, or consuming cannabis products elsewhere is inadvisable. Although busts are rare, legally you're allowed to possess only 28 grams for personal use. Bear in mind, also, that while there's a lively and growing trade in cocaine and herion, possession of either could mean a stay in one of The Netherland's lively and growing prisons. For drug-related problems, the Drug Advice Center, Keisergracht 812 (Mon.-Fri. 1:00-3:00pm; phone: 23-78-65), offers help and advice.

ELDRIDGE JC; LANDFIELD PW
Cannabinoid interactions with glucocorticoid receptors in rat hippocampus.
Brain Res. 1990 Nov 26; 534(1-2): 135-41
Previous studies have found that chronic administration of delta9-tetrahydrocannabinol (THC), a psychoactive cannabinoid, can induce brain aging-like degenerative changes in hippocampal structures (e.g., pyramidal cell loss, glial reactivity). Normal aging changes in the hippocampus appear to be partly corticosteroid-dependent. Because THC is similar in molecular structure to corticosteroids (CORT), therefore, we have suggested that THC may act to induce pathology in the hippocampus through CORT receptors. The possibility of THC interactions with CORT receptors was tested more directly in the present studies. Binding of [3H]dexamethasone (DEX) to hippocampal cytosol, in vitro, was inhibited partially, but not completely, by 100-fold excess unlabeled THC and cannabidiol (CBD), a non-psychoactive cannabinoid. Even at 10,000-fold molar excess, moreover, THC could displace only 50% of radiolabeled DEX binding and CBD could inhibit only 22% of tracer binding. Scatchard plot analyses also pointed to a possible non-competitive site for cannabinoid interaction with glucocorticoid receptors. In addition, several studies utilizing the synthetic steroid RU-28362 indicated that THC interacts primarily with the type II class of glucocorticoid receptors. In a separate study, adrenalectomized rats were treated daily for 14 days with 5-10 mg/kg THC or vehicle, and examined 24 h later for [3H]CORT binding in hippocampal cytosol. In THC-treated animals, the Bmax for type II binding was reduced to a degree almost comparable to the down-regulation seen after chronic stress or high corticosteroid administration. ...

ELSOHLY MA; JONES AB; ELSOHLY HN
Cross-reactivity of selected compounds in the Abbott TDx cannabinoid assay.
J Anal Toxicol. 1990 Sep Oct; 14(5): 277-9
Immunoassay procedures, both enzyme immunoassay and radioimmunoassay, continue to be widely used to screen samples for recent marijuana use by analyzing the urine samples for 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (11-nor-delta 9-THC-9-COOH) (the major urinary metabolite of delta 9-tetrahydrocannabinol [delta 9-THC]). Using commercially available immunoassay reagents, the cross-reactivity of the antiserum utilized in Abbott's TDx cannabinoid assay (a fluorescence polarization immunoassay) was evaluated. This cross-reactivity was evaluated against a group of cannabinoids and noncannabinoid phenolic constituents of Cannabis, some cannabinoid metabolites, and other agents that appear in normal urine samples. In general, the antiserum was equally reactive toward 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid, its glucuronide, and the corresponding delta 8-isomer, which was the acid moiety utilized in standards and controls of the assay prior to January, 1990. Reduced binding to the antiserum was observed with hydroxylated derivatives of delta 9- and delta 8-THC, and the other cannabinoids, in general, exhibited limited binding potentials toward the antibody. For the noncannabinoid constituents, no binding was observed at the highest concentrations evaluated (40 mg/L).

Emrich HM; Weber MM; Wendl A; Zihl J; von Meyer L; Hanisch W
Reduced binocular depth inversion as an indicator of cannabis-induced censorship impairment.
Pharmacol.Biochem.Behav; 1991 Nov; 40(3); P 689-90
Measurements of binocular depth inversion using a stereoscopic slide projection with polarized light were performed in healthy volunteers before and after cannabis intake. Since binocular depth inversion represents an illusion occurring in the perception of semantically meaningful objects projected in a 3-D inverted fashion, the hypothesis can be tested that cannabis-induced 'psychedelic states' represent a condition in which the human CNS is unable to correct implausible perceptual hypotheses. The data demonstrate a strong cannabis-induced impairment of binocular depth inversion.

EREMENKO AV; UVAROVA IS; KUROCHKIN IN
Vliianie del'ta-9-tetragidrokannabinola na retseptornye i fiziko-khimicheskie svoistva membran golovnogo krys. [The effect of delta-9-tetrahydrocannabinol on the receptor and physicochemical properties of the membranes in the rat brain]
Biull Eksp Biol Med. 1990 Nov; 110(11): 497-9
It has been demonstrated that delta-9-THC does not affect the specific binding of 3H-IQNB, 3H-DAGO and 3H-dihydroalprenolol, decreases the level of specific binding 3H-LSD and 3H-spiperone, a 2-3-fold increase in the total and nonspecific binding being observed in this case, and also increases the microviscosity of the rat obtain membranes and disrupts lipid-protein interactions. Increasing the microviscosity of membranes by other method (lipid peroxidation) differently affects the binding of radioactively labeled ligands with the membranes from rat brain.

EVANS EB; WENGER GR
The effects of cocaine in combination with other drugs of abuse on schedule-controlled behavior in the pigeon.
Pharmacol Biochem Behav. 1990 Oct; 37(2): 349-57
The present experiment sought to provide information regarding the consequences of combining cocaine with other drugs of abuse. The effects of cocaine alone and in combination with d-amphetamine, caffeine, morphine or delta-9-tetrahydrocannabinol were determined in five male white Carneaux pigeons responding under a multiple fixed-ratio 30, fixed-interval 600 schedule (mult FR FI). Drug interactions were studied by redetermining the cocaine dose-response curve in the presence of various fixed doses of the other drugs. Under the mult FR FI schedule, when cocaine (1 to 10 mg/kg) was combined with inactive doses of d-amphetamine (0.1, 0.3, 1.0, and 1.8 mg/kg), caffeine (10, 30, and 100 mg/kg), morphine (0.3, and 1.0 mg/kg), and delta-9-tetrahydrocannabinol (0.1 mg/kg), the FR and FI response rate dose-response curves were not shifted relative to the cocaine-alone curves. When cocaine was combined with an active dose of a drug which decreased response rate when given alone (0.3 mg/kg delta-9-tetrahydrocannabinol and 3 mg/kg morphine), the position of the response rate dose-response curves shifted compared to the cocaine-alone curves. The most frequent and consistent outcome of these interactions can be described as less than or approximately equal to an effect-additive interaction. Thus, these data indicate that the potential consequences of coabusing cocaine with the drugs tested in the present experiment can most often be predicted from the effects of each drug when taken alone.

FOLTZ RL; SUNSHINE I
Comparison of a TLC method with EMIT and GC/MS for detection of cannabinoids in urine.
J Anal Toxicol. 1990 Nov Dec; 14(6): 375-8
Urine specimens were analyzed in parallel with a new TLC method, an EMIT assay, and a reference GC/MS method. At a 9-carboxy-THC cutoff of 20 ng/mL, the TLC method correctly identified 92% of the positive urines and 97% of the negative urines. In contrast, only 63% of the urine specimens shown by GC/MS to contain greater than 20 ng/mL of 9-carboxy-THC were identified as positive by the EMIT d.a.u. assay at the 100-ng/mL cannabinoid cutoff.

Friedrich G; Leber D; Weigend M
[Urine checks as a supportive measure with drug abuse patients to supplement current therapy models]
Beitr-Gerichtl-Med; 1991; 49; P 325-31
Urine samples of 120 heroin-addicted probands who had to take part in urinanalysis tests were analysed during a 26 months' period. Up to 7 substances (morphine/diamorphie, codeine, cocain, LSD, cannabinoides, barbiturates and amphetamines) were tested. The results were compared to the results of a group of 177 cannabies-smokers. The purpose of this study was to find out in how far urinanalysis tests can change drug-consuming behaviour. More than 80% of the cannabis-smokers showed evidently a decrease of THC-positive urine samples at the end of the investigation period. Only about 13% had positive samples during the whole period. 12 out of 120 heroin-addicted probands (= 10%) had morphine-positive urine samples at the beginning of investigations. For 104 out of 1423 tested samples (46 probands) an unmistakable distinction between morphine/diamorphine- or codeine-intake was not possible because the concentrations found were too low. About 20% of the samples indicated a shift to a substitutional used drug like codeine. Further more a slightly significant increase of cannabis-intake was to be observed.

FRIEDRICH G; NEPITA W; ANDRE T
Serumtestosteronkonzentrationen bei Cannabis- und Opiatkonsumenten. [Serum testosterone concentrations in cannabis and opiate users]
Beitr Gerichtl Med. 1990; 48: 57-66
The object of this study was to establish possible influences of long-term cannabis usage on plasma testosterone levels. The plasma testosterone levels of 66 male Pakistani who for years had smoked cannabis daily or drank cannabis regularly where measured after chronic and acute intake of the drug and compared with a material of 41 normal controls, i.e. persons who did not use cannabis. An evaluation of the results showed that there were no significant differences between the two groups. No influence of long-term cannabis usage on plasma testosterone levels was found. Furthermore we wished to find out wether long-term heroin abuse showed an effect on plasma testosterone levels. The concentrations of testosterone in the plasma of 102 heroin addicts assigned to a Methadone Program were measured and compared with the values of 29 male healthy students as controls. Plasma testosterone levels were found to be significantly decreased in heroin addicts as compared to controls.

GERARD C; MOLLEREAU C; VASSART G; PARMENTIER M
Nucleotide sequence of a human cannabinoid receptor cDNA.
Nucleic Acids Res. 1990 Dec 11; 18(23): 7142
[NO ABSTRACT] cannabinoid receptor

Gerler, Edwin R; Moorhead, Stephen
Drug information: The facts about drugs and where to go for help. Special Issue: Drug abuse prevention.
Elementary School Guidance and Counseling; 1988 Dec Vol 23(2) 139-145
Presents information about commonly abused drugs (alcohol, cannabis, stimulants, inhalants, cocaine, psychedelics, depressants, narcotics, and designer drugs), their effects, and evidence of abuse. Sources of additional drug information are given, including a list of addresses that provide free or inexpensive pamphlets or brochures.

Gottlieb, Adam.
The Art and Science of Cooking with Cannabis
Twentieth Century Alchemist, 1974. 79 p.

GRAHAM K; KOREN G
Characteristics of pregnant women exposed to cocaine in Toronto between 1985 and 1990.
Can Med Assoc J. 1991 Mar 1; 144(5): 563-8
OBJECTIVE: To determine the characteristics of pregnant women exposed to cocaine. DESIGN: Case-control study. SETTING: Women attending the Motherisk Program, Hospital for Sick Children, Toronto, from September 1985 to March 1990. PATIENTS: All women who had admitted using cocaine before or during pregnancy. Of the two control groups the first comprised women who had admitted using cannabinoids but not cocaine before or during pregnancy and the second those who attended the clinic just before the cocaine case but who had not used illicit drugs. OUTCOME MEASURES: Age, marital status, ethnic background, number of pregnancies, children and elective or spontaneous abortions, socioeconomic status of woman and male partner, alcohol use, cigarette use, frequency of cocaine use and total amount taken. MAIN RESULTS: Of the 1625 women 91 (5.6%) admitted to using cocaine: 86 during the current pregnancy, 3 before the current pregnancy, 1 before planning a pregnancy and 1 during a previous pregnancy. None of the cocaine users were considered to be addicts; only 20% had used the drug more than 10 times. A total of 74 women used cannabinoids only. The mean age of the cocaine users was 27.1 (standard deviation [SD] 5.3) years; this was significantly lower than that of the control subjects (30.5 [SD 5.2] years) (p less than 0.001). More of the cocaine users than of the women in either of the two control groups were single (60% v. 38% and 14%, p less than 0.001). The cannabinoid users had significantly higher parity and the nonusers a significantly lower incidence of elective abortions than the cocaine users. The cocaine users had a significantly lower socioeconomic status than the control subjects (p less than 0.001); similarly, the male partners of the cocaine users had a significantly lower socioeconomic status than the partners of the control subjects (p = 0.001). CONCLUSIONS: Pregnant cocaine users who seek drug counselling represent a unique risk group, with clustering of factors such as alcohol and cigarette use and low socioeconomic status that compound the risk to the fetus. New strategies should be explored to identify such women, especially addicts, in their communities and to urge them to seek counselling and treatment.

GUHA, D; PRADHAN, S N
Effects of mescaline, D9-tetrahydrocannabinol and pentobarbital on the auditory evoked responses in the cat.
Neuropharmacology; 1974 Aug Vol 13(8) 755-762
Effects of intraperitoneal mescaline, D9-tetrahydrocannabinol (THC), and pentobarbital were studied on the peak latency, area, and amplitude of the waves of the average auditory evoked potentials in restrained conscious cats. Mescaline caused a significant increase in peak latency, area, and amplitude of these waves. The onset of these changes was within 10-40 min, and their duration ranged between 90-180 min. THC also caused a marked increase in peak latency, area, and amplitude. The effects of THC had its onset within 40-105 min and lasted for more than 120-180 min. Pentobarbital also caused an increase in the peak latency, area, and amplitude of these waves within 5-7 min. The peak effect occurred within 10-15 min and lasted for more than 100-120 min. These effects of the hallucinogens, mescaline and THC thus appear to resemble those of pentobarbital, a central nervous system depressant; however, the mechanism of their actions differs.

Hallucinogenes et Societe: cannabis et peyotl: phenomenes culturels et mondes de l'imaginaire. by Patrick Allain. Payot, Paris 1973. 191 pages. velobound in Two French Books on Peyote. [box v4]

HARTNOLL, RICHARD; MITCHESON, MARTIN
Attitudes of young people towards drug use.
Bulletin on Narcotics; 1973 Apr-Jun Vol 25(2) 9-24
Surveys studies of young people's attitudes toward drugs. Among school children a more positive attitude towards amphetamine, the most commonly used drug, is prevalent. However LSD and opiates are named as harmful by school children as well as by other users. Drug users think of themselves as 'interesting' people and may look upon drugs as additional 'enrichment.' Users are seriously misinformed about drugs. Users are more precocious in their behavioral development. In general, the drug culture frowns upon 'heavy' use. LSD and cannabis are favored in the 'underground' culture and amphetamines are rejected. Drugs are part of modern life, and proper education, by credible authorities, as part of the health curriculum in schools will help reduce drug abuse.

HARVEY DJ; BROWN NK
In vitro metabolism of delta-11-tetrahydrocannabinol in the mouse, rat, guinea pig, rabbit, hamster, gerbil and cat.
Comp Biochem Physiol C. 1990; 96(1): 65-9
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.

HARVEY DJ; BROWN NK
Metabolites of the 1',2'-dimethylheptyl analogue of delta-8-tetrahydrocannabinol in the mouse and their identification by gas chromatography/mass spectrometry.
Biomed Environ Mass Spectrom. 1990 Oct; 19(10): 619-27
Metabolism of the 1,2-dimethylheptyl analogue of delta-8-tetrahydrocannabinol (delta-8-DMHP) was studied in vitro using mouse hepatic microsomes and in vivo in mouse liver. Metabolites were extracted with ethyl acetate, concentrated by chromatography on Sephadex LH-20 and examined by low-resolution mass spectrometry as trimethylsilyl (TMS), (2H9)TMS and methyl ester/TMS derivatives. Reduction of metabolites with lithium aluminium deuteride also provided structural information. The electron-impact-induced mass spectrum of the TMS derivative of DMHP differed from that of its unbranched side-chain analogues in that prominent ions were produced by fragmentation of the side-chain at the expense of the retro-Diels-Alder fragmentation that was prominent in the spectra of the latter compounds. This, however, was found to reduce the relative abundance of ions diagnostic of side-chain hydroxy substitution in the spectra of the metabolites. In vitro, the only significant metabolite was 11-hydroxy-delta-8-DMHP. This is in contrast with metabolism of the corresponding delta-8-tetrahydrocannabinol (delta-8-THC, n-C5-side-chain) where a number of other monohydroxy metabolites are produced. Fifteen metabolites were found in vivo, of which nine were identified. Mass spectral information was not sufficient to determine the position of one of the hydroxy groups in the other six metabolites. The major site of hydroxylation was at C-11 and the resulting hydroxy metabolite was oxidized to delta-8-DMHP-11-oic acid. In this respect metabolism paralleled that of delta-8-THC. Dihydroxylation of the double bond also occurred, presumably via the epoxide. ...

HARVEY DJ; SAMARA E; MECHOULAM R
Urinary metabolites of cannabidiol in dog, rat and man and their identification by gas chromatography-mass spectrometry.
J Chromatogr. 1991 Jan 2; 562(1-2): 299-322
Urinary metabolites of cannabidiol (CBD), a non-psychoactive cannabinoid of potential therapeutic interest, were extracted from dog, rat and human urine, concentrated by chromatography on Sephadex LH-20 and examined by gas chromatography-mass spectrometry as trimethylsilyl (TMS), [2H9]TMS, methyl ester-TMS and methyloxime-TMS derivatives. Fragmentation of the metabolites under electron-impact gave structurally informative fragment ions; computer-generated single-ion plots of these diagnostic ions were used extensively to aid metabolite identification. Over fifty metabolites were identified with considerable species variation. CBD was excreted in substantial concentration in human urine, both in the free state and as its glucuronide. In dog, unusual glucoside conjugates of three metabolites (4'- and 5'-hydroxy- and 6-oxo-CBD), not excreted in the unconjugated state, were found as the major metabolites at early times after drug administration. Other metabolites in all three species were mainly acids. Side-chain hydroxylated derivatives of CBD-7-oic acid were particularly abundant in human urine but much less so in dog. In the latter species the major oxidized metabolites were the products of beta-oxidation with further hydroxylation at C-6. A related, but undefined pathway resulted in loss of three carbon atoms from the side-chain of CBD in man with production of 2'-hydroxy-tris,nor-CBD-7-oic acid. Metabolism by the epoxide-diol pathway, resulting in dihydro-diol formation from the delta-8 double bond, gave metabolites in both dog and human urine. It was concluded that CBD could be used as a probe of the mechanism of several types of biotransformation; particularly those related to carboxylic acid metabolism as intermediates of the type not usually seen with endogenous compounds were excreted in substantial concentration.

HAVER VM; ROMSON JL; SADRZADEH SM
Semiquantitation of cannabinoid immunoassays? A reexamination of the EMIT 20-ng/mL assay.
J Anal Toxicol. 1991 Mar Apr; 15(2): 98-100
Concerns regarding the ability to semiquantitate drugs-of-abuse urine immunoassay results, particularly THC-COOH, prompted us to reexamine EMIT results. The Syva EMIT d.a.u. cannabinoid 20-ng/mL assay was performed on the Cobas Bio centrifugal analyzer, and positive samples were confirmed by Toxi-Lab or GC/MS. Of 39 specimens tested, 17 were confirmed positive. However, four specimens were not accurately semiquantitated by EMIT. These four had very high levels (greater than 100 ng/mL) of the primary metabolite but yielded EMIT results between the low and medium calibrator (20-75 ng/mL). Linearly studies confirmed that the absorbance changes with the EMIT immunoassay plateau near the medium calibrator. In addition, we obtained false positive EMIT results due to sample carryover when samples containing 500 ng/mL (or greater) of THC-COOH preceded a negative specimen. Significant carryover was not observed when concentrations up to 1,300 ng/mL were used with the 100-ng/mL immunoassay, and this effect may be explained by the higher cutoff used. Because EMIT cannabinoid results on the Cobas Bio analyzer can be affected by carryover and a hook effect, they should not be reported even semiquantitatively.

HEISHMAN SJ; HUESTIS MA; HENNINGFIELD JE; CONE EJ
Acute and residual effects of marijuana: profiles of plasma THC levels, physiological, subjective, and performance measures.
Pharmacol Biochem Behav. 1990 Nov; 37(3): 561-5
Three experienced marijuana smokers participated in four 2-day experimental sessions in which they smoked either 0, 1, or 2 marijuana cigarettes containing 2.57% delta 9-tetrahydrocannabinol (THC) at two different times on the first day. A battery of physiological, subjective, and performance measures was repeated throughout day 1 to assess acute effects and on day 2 to measure any residual effects of marijuana. Blood samples were also repeatedly collected to examine the relationship between plasma levels and pharmacological effects of THC. Acutely, marijuana increased heart rate and subjective ratings of drug effects and slightly impaired performance on a circular lights task in all subjects. Performance was also impaired (decreased accuracy and increased response time) on serial addition/subtraction and digit recall tasks on day 1 in two subjects. On day 2, tachycardia and subjective effects of marijuana were not observed. Performance remained impaired on the arithmetic and recall tasks on day 2, although the decrements were not as large as those observed on day 1. In general, plasma THC levels covaried with the other measures. These preliminary results suggest that marijuana can adversely affect complex human performance up to 24 hours after smoking.

HERKENHAM M; LYNN AB; JOHNSON MR; MELVIN LS; DE COSTA BR; RICE KC
Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study.
J Neurosci. 1991 Feb; 11(2): 563-83
A potent, synthetic cannabinoid was radiolabeled and used to characterize and precisely localize cannabinoid receptors in slide-mounted sections of rat brain and pituitary. Assay conditions for 3H-CP55,940 binding in Tris-HCl buffer with 5% BSA were optimized, association and dissociation rate constants determined, and the equilibrium dissociation constant (Kd) calculated (21 nM by liquid scintillation counting, 5.2 nM by quantitative autoradiography). The results of competition studies, using several synthetic cannabinoids, add to prior data showing enantioselectivity of binding and correlation of in vitro potencies with potencies in biological assays of cannabinoid actions. Inhibition of binding by guanine nucleotides was selective and profound: Nonhydrolyzable analogs of GTP and GDP inhibited binding by greater than 90%, and GMP and the nonhydrolyzable ATP analog showed no inhibition. Autoradiography showed great heterogeneity of binding in patterns of labeling that closely conform to cytoarchitectural and functional domains. Very dense 3H-CP55,940 binding is localized to the basal ganglia (lateral caudate-putamen, globus pallidus, entopeduncular nucleus, substantia nigra pars reticulata), cerebellar molecular layer, innermost layers of the olfactory bulb, and portions of the hippocampal formation (CA3 and dentate gyrus molecular layer). Moderately dense binding is found throughout the remaining forebrain. Sparse binding characterizes the brain stem and spinal cord. Densitometry confirmed the quantitative heterogeneity of cannabinoid receptors (10 nM 3H-CP55,940 binding ranged in density from 6.3 pmol/mg protein in the substantia nigra pars reticulata to 0.15 pmol/mg protein in the anterior lobe of the pituitary). The results suggest that the presently characterized cannabinoid receptor mediates physiological and behavioral effects of natural and synthetic cannabinoids, because it is strongly coupled to guanine nucleotide regulatory proteins and is discretely localized to cortical, basal ganglia, and cerebellar structures involved with cognition and movement.

HOLLISTER LE; GILLESPIE HK
The benzodiazepine receptor antagonist, flumazenil does not block clinical effects of delta-9-tetrahydrocannabinol.
Life Sci. 1990; 47(18): 1655-60
Fifteen normal volunteer men were given intravenous doses of 2 mg of delta-9-tetrahydrocannabinol (THC) and 3 were given doses of 0.5 mg. Five, 15 and 30 minutes later, they were given intravenous doses of the benzodiazepine receptor antagonist, flumazenil. Doses of this compound ranged between 0.1 and 3.2 mg for single doses and 0.7 and 6.4 mg for total doses, being increased progressively with each successive subject, until dose-ranging was completed in 10 subjects. After that 5 subjects were given doses of 2 mg of THC on two occasions, followed by either doses of 3.2 or 6.4 mg flumazenil or placebo, administered under blind conditions. Three subjects were treated with 0.5 mg doses of THC followed by 3.2 mg of flumazenil or placebo under similar conditions. Despite doses of the antagonist which would have been adequate to reverse the effects of substantial doses of benzodiazepines, little ameliorative action was observed on the level of intoxication or the degree of conjunctival injection, two quite reliable clinical indicators of THC action. The benzodiazepine receptor does not seem to play any significant role in the psychoactive actions and conjunctival injection produced by THC.

HOLSTEN, FRED
Flashbacks: A personal follow-up.
Archiv fur Psychiatrie und Nervenkrankheiten; 1976 Vol 222(4) 293-304
Studied 91 young drug users who had sought help at a psychiatric hospital to determine the frequency and degree of seriousness of flashbacks in these Ss and to determine whether these reactions occur only in users of cannabis and LSD or whether they are also experienced by users of other drugs. It was found that 53 of the Ss had experienced flashbacks. This was true for approximately 50 of 65 Ss who had used LSD, and also for users of organic solvents and cannabis. As many as 38% of the Ss were severely incapacitated by their flashbacks. On a personal follow-up 11/2-4 yrs after the 1st therapeutic contact, 35 Ss were still troubled by flashbacks. Generally, the reactions were less intense than at the time of the first contact. No relation between the flashbacks and protracted psychotic development could be established. The overall clinical and social course was worse for Ss with flashbacks than for the rest of the sample. Ss still bothered by flashbacks used drugs and alcohol as sedatives to a greater extent than the rest.

HOLT HANSEN, KRISTIAN
Extraordinary experiences during cross-modal perception.
Perceptual and Motor Skills; 1976 Dec Vol 43(3) 1023-1027
Nine university students were requested to perceive simultaneously the taste of beer and a rhythmic sound, the pitch of which could be varied. The frequencies at which Ss experienced harmony between the taste and the sound were determined. At the pitch of harmony, Ss reported characteristic experiences (e.g., optimum taste of the beer, rhythmic sensations in the head, and tickling sensations in the jaws and the mouth). Three Ss also reported experiences resembling those described by persons under the influences of such drugs as mescaline, psilocybin, LSD, and cannabis.

HOWLETT AC; BIDAUT RUSSELL M; DEVANE WA; MELVIN LS; JOHNSON MR; HERKENHAM M
The cannabinoid receptor: biochemical, anatomical and behavioral characterization.
Trends Neurosci. 1990 Oct; 13(10): 420-3
The actions of the active principle of marihuana, delta 9-tetrahydrocannabinol, are mimicked by synthetic cannabinoid agonists showing high potency and enantio-selectivity in behavioral assays. These drugs have been used to characterize cannabinoid receptor binding, biochemistry and pharmacology, leading to a better understanding of the effects of cannabinoids in the CNS of humans and experimental animals.

HOWLETT AC; JOHNSON MR; MELVIN LS
Classical and nonclassical cannabinoids: mechanism of action--brain binding.
NIDA Res Monogr. 1990; 96: 100-11
[NO ABSTRACT] cannabinoids

HOWLETT AC
Reverse pharmacology applied to the cannabinoid receptor.
Trends Pharmacol Sci. 1990 Oct; 11(10): 395-7
[NO ABSTRACT] cannabinoid receptor

HUTCHINGS DE; DOW EDWARDS D
Animal models of opiate, cocaine, and cannabis use.
Clin Perinatol. 1991 Mar; 18(1): 1-22
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. ...

HUTCHINGS DE; FICO TA; BANKS AN; DICK LS; BRAKE SC
Prenatal delta-9-tetrahydrocannabinol in the rat: effects on postweaning growth.
Neurotoxicol Teratol. 1991 Mar Apr; 13(2): 245-8
Either 15 or 30 mg/kg of delta-9-tetrahydrocannabinol (delta-9-THC) was administered from Day 2 through Day 22 of gestation. Pair-fed and nontreated groups served as controls and all treated and control litters were fostered at birth to untreated dams. When weighed at 57-60 days of age, pair-fed controls were significantly heavier than the nontreated, whereas the treated animals were intermediate between the controls. These findings are discussed with respect to nutritional studies that have reported postnatal growth enhancement following prenatal maternal undernutrition and the possibility that prenatal delta-9-THC inhibits this effect.

IMADE AG; EBIE JC
A retrospective study of symptom patterns of cannabis-induced psychosis.
Acta Psychiatr Scand. 1991 Feb; 83(2): 134-6
The aim of this study was to find out whether there are any similarities between cannabis psychosis on the one hand and schizophrenia and mania on the other, and to delineate any consistency in the pattern of clinical symptoms of cannabis psychosis. Relevant data were collected from patient's case-notes depicting biographical information and the frequencies of mental symptoms. Age and duration in hospital agreed between the 3 groups. Although several significant differences were recorded in the distribution of mental symptoms, it was not possible to demonstrate a consistent pattern of symptoms typical of cannabis psychosis.

KAFERSTEIN H; STICHT G
Vergleichende Untersuchungen zum Drogennachweis mit neueren immunologischen Methoden. [Comparative studies of drug detection using recent immunologic methods]
Beitr Gerichtl Med. 1990; 48: 51-6
150 urine samples which we received from the criminal investigation department were measured with EMIT cannabis 20 and EMIT cannabis 50 reagents by EMIT Autolabsystem and especially with the immunoassay analyzer ETS by Syva Diagnostica. The confirming analyses were performed by GC-MS. If only cases are considered which are positive with cannabis 20 containing at least 10 ng 11-Nor-delta-9-THC-9-carboxylic acid in urine, there will be a negative result of 18.8% with EMIT 50. This appears to be unreasonably high. Some of these cases were also tested with Abuscreen ONTRAK-reagents. With this method the cut off for cannabis with 100 ng/ml urine is far too high but can be lowered essentially by taking a larger urine sample.

KIOSSES BW; TAHIR SK; KALNINS VI; ZIMMERMAN AM
The effects of delta-9-tetrahydrocannabinol on actin microfilaments.
Cytobios. 1990; 63(252): 23-9
Fluorescence staining with rhodamine phalloidin specific for F-actin was employed to examine the effects of delta-9-tetrahydrocannabinol (THC) on the distribution of microfilaments in kangaroo rat epithelial cells (PtK2) and rabbit aortic endothelial cells (RAE). PtK2 cells were more sensitive to THC treatment than RAE cells. Exposure of PtK2 cells to 10 microM THC for 2 h disrupted the microfilament network. After treatment with 20 microM THC for 2 h there was a loss of cell-to-cell contact between PtK2 cells, and at 30 microM THC, the cells started to detach from the substratum. In contrast, microfilament disorganization but not cell detachment was observed in RAE cells at THC concentrations of 80 and 100 microM. The possible mechanisms which may account for the changes in the microfilament system are discussed.

KLEIN TW; KAWAKAMI Y; NEWTON C; FRIEDMAN H
Marijuana components suppress induction and cytolytic function of murine cytotoxic T cells in vitro and in vivo.
J Toxicol Environ Health. 1991 Apr; 32(4): 465-77
Killer lymphocytes play a major role in host defense against tumors and infectious diseases. Previously, we reported that delta-9-tetrahydrocannabinol (THC) and II-hydroxy-delta-9-tetrahydrocannabinol (II-hydroxy-THC) suppressed the cytolytic activity of cultured natural killer (NK) cells. Also, we showed that the drugs appeared to be affecting a stage in the killing process subsequent to the binding of the killer cell to the target cell. In the present report, we have extended these studies to an examination of the effect of cannabinoids on the activity of cytotoxic T lymphocytes (CTLs). The cytolytic activity of CTLs generated by cocultivation with either allospecific stimulators or TNP-modified-self stimulators were suppressed by both THC and II-hydroxy-THC treatment. Allospecific CTLs generated in vivo were also inhibited by an in vitro exposure to either THC or II-hydroxy-THC, and the sensitivity of these cells to drug effects appeared to be greater than the sensitivity of the in vitro generated CTLs. Suppression of cytolytic function by THC and II-hydroxy-THC was maximal after a 4-h drug treatment, suggesting that the drug effects were inducible and therefore required a finite period of time to develop maximally. As seen in previous studies involving NK cells, drug treatment of mature CTLs appears to have little effect on the binding capacity of these cells for the target. However, the maximal killing capacity of the cells and the frequency of CTLs were significantly reduced by drug treatment. In addition to suppressing the cytolytic activity of mature effector CTLs, we also show that drug treatment inhibits both the proliferation of lymphocytes responding to an allogeneic stimulus and the maturation of these lymphocytes to mature CTLs. Similarly, CTL activity developing in vivo could be inhibited by THC injection. These results suggest that CTLs are inhibited by cannabinoids by at least two mechanisms. First, the cytolytic activity of mature killers is suppressed at some point beyond the binding to the target cell. Second, the cannabinoids appear to suppress the normal development of these mature effector cells from less mature precursor cells.

KUHN, D M; APPEL, J B; GREENBERG, I
An analysis of some discriminative properties of d-amphetamine.
Psychopharmacologia; 1974 Vol 39(1) 57-66
Trained and tested 6 male Sprague-Dawley albino rats on a 2-lever discrimination task based upon the presence or absence of dextroamphetamine sulfate (1.0 mg/kg). This compound produced strong discriminative cues. A dose-effect function was then ascertained, and the discriminative effective dose was found to be .23 mg/kg amphetamine. To determine the effective duration of amphetamine action, the interval between injection and testing was varied; it was found that the discriminative effects of the drug began to dissipate between 60 and 90 mins postinjection. To compare the discriminative cues of other drugs with those of amphetamine, injections of LSD, psilocybin, tetrahydrocannabinol, mescaline, and caffeine were given during extinction. In all cases, Ss responded predominantly on the saline-related lever. Only methamphetamine produced dextroamphetamine-like responding. Alpha-methyl-para-tyrosine, a compound which depletes brain catecholamines, disrupted the amphetamine-saline discrimination.

KUMAR AM; HANEY M; BECKER T; THOMPSON ML; KREAM RM; MICZEK K
Effect of early exposure to delta-9-tetrahydrocannabinol on the levels of opioid peptides, gonadotropin-releasing hormone and substance P in the adult male rat brain.
Brain Res. 1990 Aug 13; 525(1): 78-83
The effects of neonatal exposure to delta-9-tetrahydrocannabinol (THC) on the adult animal brain neurochemistry and pain perception were evaluated. Newborn rat pups were culled to a litter size of 8 (males and females) and treated either with THC (2 mg/kg) or oil (control) daily, during days 1-4 after birth. After weaning, the THC-treated males were housed 4 per cage. During the juvenile period (day 50), the THC-treated animals exhibited significantly lower baseline tail-flick values (a measure of pain perception) than the control. However, as adults, the THC-treated animals exhibited significantly higher sensitivity to pain following 5 mg/kg morphine challenge. Furthermore, the THC-treated animals had significantly elevated beta-endorphin and methionine-enkephalin levels in almost all the brain areas sampled for the study. In addition, the neonatally THC-treated rats exhibited significantly higher levels of substance P (SP) and significantly lower levels of gonadotropin releasing hormone (GnRH) in the anterior hypothalamus-preoptic area. The SP and GnRH levels did not differ among the THC-treated and control animals in the medial basal hypothalamus. The results of this study indicate that even a very low dose of THC administered during the neonatal period has a long-lasting effect on the brain neurochemistry. In particular, neonatal administration of THC appears to alter functioning of the endogenous opioid system.

La Barre, Weston.
[Review] Anthropological Views of Cannabis.
(1977)

LANCZ G; SPECTER S; BROWN HK
Suppressive effect of delta-9-tetrahydrocannabinol on herpes simplex virus infectivity in vitro.
Proc Soc Exp Biol Med. 1991 Apr; 196(4): 401-4
Delta-9-Tetrahydrocannabinol (THC) was found to reduce the infectivity of herpes simplex virus and was without effect against adenovirus type 2 or poliovirus. The effective THC concentration resulting in an 80% decrement in virus viability was dependent upon the presence or absence of serum in the incubation mixture, as a 5% serum concentration decreased the drug activity by approximately 50-fold. THC-mediated inactivation of herpes simplex virus was both time and dose dependent and did not result in virion disassembly or clumping. The THC-related effect was not influenced by the pH of the suspending medium, suggesting that the mechanism of inactivation differed from that associated with the thermal inactivation of the virus. Thus, the data suggest that THC preferentially reduces the infectivity of the enveloped herpes simplex virus, and that this activity is modulated by the presence of serum proteins.

LEIKIN JB; KRANTZ AJ; ZELL-KANTER M; BARKIN RL; HRYHORCZUK DO
Clinical features and management of intoxication due to hallucinogenicdrugs.
Med Toxicol Adverse Drug Exp. 1989 Sep-Oct. 4(5). P 324-50.
Hallucinogenic drugs are unique in that they produce the desired hallucinogenic effects at what are considered non-toxic doses. The hallucinogenic drugs can be categorised into 4 basic groups: indole alkaloid derivatives, piperidine derivatives, phenylethylamines and the cannabinols. The drugs reviewed include lysergic acid diethylamide(LSD), phencyclidine (PCP), cocaine, amphetamines, opiates, marijuana, psilocybin, mescaline, and 'designer drugs.' Particularly noteworthy is that each hallucinogen produces characteristic behavioural effects which are related to its serotonergic, dopaminergic or adrenergic activity. Cocaine produces simple hallucinations, PCP can produce complex hallucinations analogous to a paranoid psychosis, while LSD produces a combination of hallucinations, pseudohallucinations and illusions. Dose relationships with changes in the quality of the hallucinatory experience have been described with amphetamines and, to some extent, LSD. Flashbacks have been described with LSD and alcohol. Management of the intoxicated patient is dependent on the specific behavioural manifestation elicited by the drug. The principles involve [] differentiating the patient's symptoms from organic (medical or toxicological) and psychiatric aetiologies and identifying the symptom complex associated with the particular drug. Panic reactions may require treatment with a benzodiazepine or haloperidol. Patients with LSD psychosis may require an antipsychotic. Patients exhibiting prolonged drug-induced psychosis may require a variety of treatments including ECT, lithium and l-5-hydroxytryptophan. Refs: 233.

LEON CARRION J
Mental performance in long-term heavy cannabis use: a preliminary report.
Psychol Rep. 1990 Dec; 67(3 Pt 1): 947-52
Mental performance of 23 male chronic cannabis users was measured on the 1958 Wechsler Adult Intelligence Scale and compared with scores of a control group. Analysis showed significant differences on nine of the 14 scores especially those indicating capacity for compromise, the elaboration of adequate judgments, and the capacity of verbalization and communication.

LEONARD, HENRIETTA L; RAPOPORT, JUDITH L
Relief of Obsessive-Compulsive Symptoms by LSD and Psilocin.
American Journal of Psychiatry; Vol. 144(9) Sept 1987 p 1239-1240
An unusual case of a patient with both obsessive-compulsive disorder and multiple substance abuse provides strongly suggestive support for a role of the serotonin system in obsessive-compulsive disorder. Adam, a 17-year-old white high school senior, had severe obsessive-compulsive disorder that had begun at age 8. Since age 13, his mind had been so preoccupied by obsessive thoughts that he was unable to do any task spontaneously. All acts had to be done in a certain way and a certain number of times. He showered by lathering the soap 22 times. He was unable to walk down a corridor unless he tapped the correct amount of times on the wall and could not complete any school assignments because written alphabet letters had to end 'in a certain way going up.' He was acutely aware of the irrationality of these thoughts and rituals. Since the age of 14, Adam had extensively abused drugs; he had observed three different kinds of effects on his obsessive-compulsive disorder symptoms from these substances: specific selective improvement, nonspecific improvement, and specific worstening. LSD (which he had used more than 100 times) made his obsessive thoughts slightly worse for an hour, followed by total remission for 4-5 hours. 'Mushroom' (psilocin) and mescaline, which he had used about 20 times each, also made the thoughts totally disappear. Cocaine (used more than 100 times) and amphetamine (used about 15 times) worstened the thoughts, so that he would spend hours touching the walls 22 times. In contrast to these selective changes, cannabis, phencyclidine, barbiturates, methaqualone, morphine, codeine, and alcohol did not change the frequency or the intensity of the obsessive thoughts but just 'made everything easier to bear'. The psychedelic drugs LSD, psilocin, and mescaline act on the serotonergic system, both pre- and postsynatptically, at several sites within the brain. Morphine, codeine, and possibly phencyclidine affect opiate receptors, and their effects are not thought to be primarily related to monoamine systems. Amphetamine and cocaine, which worsened the patient's thoughts, both release and block the uptake of catecholamines, resulting in a general stimulation of the CNS. Cannabis's mechanism of action is not known, but it does not act directly on monoamines. Barbiturates and alcohol, which are CNS depressants, affect both excitatory and inhibitory synaptic transmission, with complex CNS effects not tied directly to monoaminergic systems. The reports of this patient, who had no knowledge of biochemistry, are of great interest, as they are consistent with a serotonin hypothesis of obsessive-compulsive disorder. In addition to the well-documented efficacy of clomipramine in obsessive-compulsive disorder, augmentation of clomipramine by L-tryptophan and lithium has been reported. Furthermore, response to clomipramine has been correlated with higher pretreatment platelet serotonin concentration.

LEVY JA; HEPPNER GH
Immunosuppression by marihuana and its cannabinoid constituents.
J Immunopharmacol. 1980; 2(2): 159-77
[NO ABSTRACT] Marijuana and immunosupression.

Li, Hui-Lin.
An Archaeological and Historical Account of Cannabis in China.
Economic Botany 28:437-448. (1974)

Li, Hui-Lin.
The Origin and Use of Cannabis in Eastern Asia: Linguistic-Cultural Implications.
Economic Botany 28:293-301. (1974)

LITTLE PJ; MARTIN BR
The effects of delta 9-tetrahydrocannabinol and other cannabinoids on cAMP accumulation in synaptosomes.
Life Sci. 1991; 48(12): 1133-41
The effects of delta 9-THC and other cannabinoids on cAMP levels in synaptosomes from mouse brains were investigated in order to determine whether cannabinoids produced their behavioral effects through alterations in adenylate cyclase. delta 9-THC (0.01-10 microM) did not significantly alter basal cAMP levels, whereas delta 9-THC and other cannabinoids were able to alter forskolin-stimulated cAMP levels in synaptosomes. In general, three kinds of responses were observed. Some cannabinoids displayed a modest, concentration-dependent decrease in cAMP levels, producing significant inhibition between 1-10 microM. Other cannabinoids, including delta 9-THC and delta 8-THC, appeared to produce a biphasic effect in that inhibition of cAMP was observed only at a single concentration. Finally, some analogs were unable to significantly alter forskolin-stimulated cAMP. There was not a clear relationship between the ability of the cannabinoids to alter cAMP levels in synaptosomes and the behavioral effects observed in mice. However, it was demonstrated that the analogs which are the most potent in producing cannabimimetic effects in mice were the analogs which inhibited cAMP in a concentration-dependent manner. While cannabinoids were able to alter cAMP levels in synaptosomes, the ability to alter cAMP levels does not appear to be absolutely necessary for the production of cannabinoid effects in mice.

LSD, Marijuana, Yoga, and Hypnosis. Theodore Xenophon Barber. Aldine Publishing Co. Chicago. 1970. Part A: Psychedelic Drugs and Cannabis Derivatives, pages 1-111. (photocopy velobound in anthology "Psychedelics in Society Volume Two"). [box v3]

LUTHRA YK; ESBER HJ; LARIVIERE DM; ROSENKRANTZ H
Assessment of tolerance to immunosuppressive activity of delta 9-tetrahydrocannabinol in rats.
J Immunopharmacol. 1980; 2(2): 245-56
Immunosuppression evoked by delta 9-tetrahydrocannabinol (delta 9-THC) has been a consistent finding in rats but the development of tolerance to this phenomenon has not been explored. Therefore, Fischer rats of both sexes were orally given delta 9-THC at 6 or 12 mg/kg or sesame oil as vehicle control for 5-26 days before and after I.P. antigenic stimulation with sheep red blood cells (SRBC). delta 9-THC doses were relevant to those of man and produced mild CNS-inhibition followed by CNS-stimulation, tolerance developing to both behavioral phases. The primary immune response was evaluated by determining splenic antibody-forming cells (AFC), hemagglutinin (HT) and/or hemolysin (HS) titers. Simultaneous administration of delta 9-THC and SE induced dose-related splenic atrophy and reduced AFC proliferation as well as HT and HS responses. These changes were not elicited by sesame oil. Tolerance did not develop to immunosuppression during 26 days of cannabinoid treatment. delta 9-THC given 3 days post SRBC inoculation induced immunosuppression at 12 but not 6 mg/kg. Immunosuppression was directly related to delta 9-THC rather than to non-specific debilitating factors since body weights are stable. The inductive phase of the primary immune response was most sensitive to impairment although the reproductive phase was also affected at the high dose level.

MAKRIYANNIS A; RAPAKA RS
The molecular basis of cannabinoid activity.
Life Sci. 1990; 47(24): 2173-84
Cannabinoids have been known to exhibit a wide variety of biological effects. Over the past fifty years numerous analogs were synthesized in an attempt to understand the structural requirements for each cannabinoid activity. Only recently, however, some important findings have focused new attention on this field of research. These findings include: (a) The development of novel 'non-classical' potent cannabinoid analogs which exhibit similar pharmacological profiles with their 'classical' counterparts; (b) The demonstration that there are specific cannabinoid binding sites in cell cultures as well as in mammalian brains; (c) Biophysical studies related to the interactions of cannabinoids with membranes which lead to a better understanding of those molecular properties which are required for cannabinoid activity; (d) Detailed and uniform pharmacological testing on a sizeable number of analogs allowing for a more detailed dissection of the cannabinoid effects and respective 'structure activity relationships.' The newly increased interest in cannabinoid research opens the door for a better understanding and potential treatment in cases of abuse as well as novel therapeutic opportunities through the design and synthesis of pharmacologically more selective analogs.

MAKRIYANNIS A; YANG DP; GRIFFIN RG; DAS GUPTA SK
The perturbation of model membranes by (-)-delta 9-tetrahydrocannabinol. Studies using solid-state 2H- and 13C-NMR.
Biochim Biophys Acta. 1990 Sep 21; 1028(1): 31-42
The effects of (-)-delta 9-tetrahydrocannabinol (delta 9-THC) on model phospholipid membranes were studied using solid-state 2H and 13C nuclear magnetic resonance spectroscopy. Aqueous multilamellar dispersions of dipalmitoylphosphatidylcholine with specific 2H- and 13C-labels as endogenous probes at the C7, methylene and the carbonyl groups, respectively, of the sn-2 chain were used to study the conformational and dynamic properties of the bilayer as a function of temperature and drug concentration. The drug molecule decreases the phase transition temperature of the bilayer in a concentration dependent manner up to 20 molar percent when full saturation has occurred. The 2H spectra show that delta 9-THC broadens the phase transition during which the spectra acquire a characteristic shape of a two-component system exchanging at an intermediate rate (approximately 10(6) s-1) with some liquid crystalline features. Such spectra provide information related to the melting of the phospholipid chains. At intermediate temperatures, the 13C spectra show a gel-like and a liquid-crystalline-like exchanging components and provide information about a conformational change at the phospholipid glycerol backbone occurring at or near the pretransition. The spectral composition and rate of exchange are both dependent on drug concentration. We have carried out computer simulations of the 13C spectra and obtained conformational information related to the phase transition process in the bilayer from gel to liquid crystal. Our studies show that delta 9-THC has a stronger effect on the sn-2 carbonyl near the bilayer interface than on the lipid chains and serve to describe the membrane perturbing effects of cannabinoids in molecular terms.

Marijuana Botany: An Advanced Study: The Propagation and Breeding of Dsitinctive Cannabis. Robert Connell Clarke. An/Or Press. Berkeley, CA. 1981. paperback. 198 pages. one of the best books on its topic. [box 2m]

MARTIN, PARTHENA; CONSROE, PAUL
A preliminary study of THC-LSD interactions on rabbit EEG and behavior.
Physiological Psychology; 1981 Jun Vol 9(2) 219-222
Recorded quantified cortical and hippocampal EEGs and corresponding behaviors from 4 New Zealand white rabbits who were given either acute or subacute (12-day) tetrahydrocannabinol (THC; .5 mg/kg, iv) followed by acute LSD (50 mug/kg, iv). Results indicate that acute THC did not block the stimulant effects of LSD (increases in standing and activity). However, subacute THC produced tolerance to the depressant cortical EEG (increase in delta) and behavioral (sprawling) activity of the cannabinoid and blocked some excitatory effects of LSD.

MAURER M; HENN V; DITTRICH A; HOFMANN A
Delta-9-tetrahydrocannabinol shows antispastic and analgesic effects in a single case double-blind trial.
Eur Arch Psychiatry Neurol Sci. 1990; 240(1): 1-4
A double-blind study was performed comparing 5 mg delta-9-tetrahydrocannabinol (THC) p.o., 50 mg codeine p.o., and placebo in a patient with spasticity and pain due to spinal cord injury. The three conditions were applied 18 times each in a randomized and balanced order. Delta-9-THC and codeine both had an analgesic effect in comparison with placebo. Only delta-9-THC showed a significant beneficial effect on spasticity. In the dosage of THC used no altered consciousness occurred.

McGlothlin, William H.
Hallucinogenic Drugs: A Perspective with Special Reference to Peyote and Cannabis.
Psychedelic Rev. 6:16-57. (1965)

MECHANICK, PHILIP,; ET AL
Nonmedical drug use among medical students.
Archives of General Psychiatry; 1973 Jul Vol. 29(1) 48-50
Mailed a questionnaire on illicit drug use to 1st-4th yr medical students in 1970 and 1972. 449 Ss (82%) responded in 1970 and 463 (79%) responded in 1972. Results reveal a large increase in the number of Ss who used cannabis between 1970 and 1972. Despite this greater occurrence of use, there was a marked decline in the current frequency of use among the 2 classes studied in both years, evidently due to loss of interest in taking the drug. Over the 2 years there was also a decrease in the number of Ss favoring legalization of marihuana. In both studies, relatively few Ss had ever taken LSD, mescaline, amphetamines, and barbiturates. Among Ss who had taken these drugs, interest also decreased by 1972. Findings suggest that cannabis use was prevalent in medical school irrespective of the age of the student but has now subsided.

MENKES DB; HOWARD RC; SPEARS GF; CAIRNS ER
Salivary THC following cannabis smoking correlates with subjective intoxication and heart rate.
Psychopharmacology Berl. 1991; 103(2): 277-9
A cannabis smoking trial was conducted using paid volunteers. Subjective intoxication, measured using a visual analogue scale, was compared with heart rate and with salivary delta-9-tetrahydrocannabinol (THC) levels at various times after smoking a cigarette containing 11 mg THC. Subjective intoxication and heart rate elevation were significantly correlated with the log of salivary THC. Salivary THC levels are a sensitive index of recent cannabis smoking, and appear more closely linked with the effects of intoxication than do either blood or urine cannabinoid levels.

MILLER NS; GOLD MS; KLAHR AL
The diagnosis of alcohol and cannabis dependence (addiction) in cocaine dependence (addiction).
Int J Addict. 1990 Jul; 25(7): 735-44
In two separate studies in 263 inpatients using DSM-III-R criteria for alcohol and drug dependence (addiction) we confirm the clinical experience that cocaine addicts are dependent on other drugs including alcohol. Our study finds a high prevalence of alcohol dependence and cannabis dependence in patients with cocaine dependence. As many as 89% of cocaine addicts diagnosed by DSM-III-R criteria for cocaine dependence (addiction) qualify for other alcohol and drug dependence diagnoses. Previous reports regarding alcohol and other drug use among cocaine addicts are few and inconclusive. The diagnosis of other alcohol and drug dependence in cocaine dependence has important impact on etiology, prognosis, and treatment.

MILLER NS; KLAHR AL; GOLD MS; SWEENEY K; COCORES JA
The prevalence of marijuana (cannabis) use and dependence in cocaine dependence.
N Y State J Med. 1990 Oct; 90(10): 491-2
In a retrospective and prospective study using DSM-III-R criteria for substance dependence in 232 inpatients and 51 outpatients, the clinical suspicion that cocaine addicts use other drugs including marijuana was confirmed. As many as 53% of cocaine addicts diagnosed by DSM-III-R criteria for cocaine dependence qualified for a diagnosis of cannabis dependence. The reports regarding marijuana and other drug dependence among cocaine addicts have been few and inconclusive. The diagnosis of other drug use and dependence in cocaine dependence has importance with regard to prognosis and treatment. This study found a high prevalence of marijuana (cannabis) dependence in patients with cocaine dependence.

Morningstar, Patricia C.
Thandai and Chilam: Traditional Hindu Beliefs About the Proper Uses of Cannabis.
Journal of Psychoactive Drugs 17/3:141-165. (1985)

MOSCHOVAKIS, A; ET AL
Cannabis interferes with nest-building behavior in mice.
Psychopharmacology; 1978 Vol 58(2) 181-183
Nest-building behavior has never been used to answer questions concerning the psychotomimetic effects of delta-9-tetrahydrocannabinol (THC). In this study, several fractions of cannabis and tobacco pyrolysis products were tested consecutively in the same procedure. The following drugs were injected ip under a saline-drug-saline schedule: dextroamphetamine (6 mg/kg), pentobarbital (25 mg/kg), THC (10, 5, 2.5 mg/kg), the cannabis fractions designated I-sub(S ) (water soluble products), II-sub(S ) (nonsoluble, nonvolatile products), III-sub(S ) (what is inhaled by a hashish smoker), and analogous fractions of tobacco pyrolysis products designated III-sub(B ) (what is inhaled by a common tobacco smoker), II-sub(B), and I-sub(B). The effects of THC (10 mg/kg), II-sub(S), and III-sub(S ) were similar in disrupting the normal behavioral pattern. Amphetamine, THC (5 mg/kg), and II-sub(B ) disrupted normal behavior as well. The similarity of the effects of II-sub(S ) and III-sub(S ) was unexpected in view of the different contents of cannabinoids in these fractions. Also unexpected was the similarity of the effects of THC (10 mg/kg) and III-sub(S ) (40 mg/kg containing 7% THC), as well as the activity of fraction III-sub(B).

NDOSI, N.K.
Cannabis and its health-damaging effects
The Dar es Salaam Medical Journal, v 10(2) pp. 10-12 ( 1993), Niger
CANNABIS / CANNABINOIDS / MARIJUANA ABUSE / MARIJUANA SMOKING / SUBSTANCE ABUSE / HEALTH PROMOTION / ADOLESCENT BEHAVIOR
Cannabis is derived from the plant Cannabis sativa. Bhang or marijuana might be the cheapest and most readily available form of cannabis abused mainly by adolescents and young adults in Tanzania, but concrete data is lacking. Some of the drug abusers are mentally unstable individuals who lack self criticism and adequate self restraint. When bhang is smoked, cannabinoids are readily absorbed from the lung and bound by the grey matter of the brain. Cannabinoids are psychoactive ingredients which cause complex behavioural changes with stimulant and depressed properties. This article therefore, aims at raising more awareness concerning the health-damaging consequences of bhang abuse. . African Index Medicus

PAGE, J BRYAN; FLETCHER, JACK M; TRUE, WILLIAM R
Psychosociocultural perspectives on chronic cannabis use: The Costa Rican follow-up. Special Issue: Marijuana--an update.
Journal of Psychoactive Drugs; 1988 Jan-Mar Vol 20(1) 57-65
Conducted a 4-yr follow-up of Costa Rican marihuana users and matched nonusers previously studied by W. E. Carter et al (1980). 57 of 82 Ss were available at follow-up. They completed a test battery including the Wechsler Adult Intelligence Scale (WAIS); measures of lateralized motor and tactile performance, learning and memory, sustained attention and concentration, and speeded motor planning; the Sixteen Personality Factor Questionnaire (16PF); and the Minnesota Multiphasic Personality Inventory (MMPI). Results indicate that users were slower in processing and on self-paced measures requiring sustained attention than nonusers. Anthropological findings are discussed with reference to cognitive function testing.

PEDERSEN W
Adolescents initiating cannabis use: cultural opposition or poor mental health?
J Adolesc. 1990 Dec; 13(4): 327-39
In Norway, the use of cannabis was introduced by a resourceful group of oppositional middle-class adolescents in the late 1960s. At the beginning of the 1970s there were, however, signs of a change in the recruitment of the users: youths in trouble from lower social levels gradually started to use the drug. In a prospective longitudinal study of 1311 Norwegian pupils aged 13-19, the possible links between normative and political opposition, mental health and the use of cannabis were investigated. The findings indicate that the group that experiments with cannabis, and use the drugs a few times, is still mainly characterized by a political and normative 'oppositional' engagement. Heavy users of cannabis, however, also have family problems and suffer from poor mental health. Thus, the study draws attention to the importance of distinguishing between two different clusters of longitudinal predictors for adolescent cannabis use: the first consists of subcultural opposition and certain personality traits, and seems to predict the earlier stages of use. The second consists of psychosocial problems and poor mental health. From this study one may not conclude that this second cluster predicts heavy cannabis involvement. We have, however, shown that it correlates with heavy involvement, cross-sectionally.

PEREZ REYES M
Marijuana smoking: factors that influence the bioavailability of tetrahydrocannabinol.
NIDA Res Monogr. 1990; 99: 42-62
[NO ABSTRACT] marijuana THC

PERTWEE RG; ROSS TM
Drugs which stimulate or facilitate central cholinergic transmission interact synergistically with delta-9-tetrahydrocannabinol to produce marked catalepsy in mice.
Neuropharmacology. 1991 Jan; 30(1): 67-71
In experiments in which mice were placed with their forepaws over a 4 cm high horizontal bar, delta-9-tetrahydrocannabinol (THC; 10 mg/kg i.p.) delayed descent from the bar. This effect on descent latency was markedly enhanced by physostigmine (0.05 or 0.25 mg/kg s.c.) and oxotremorine (0.04 or 0.08 mg/kg s.c.), administered immediately before THC. These interactions were attenuated by atropine (2.0 mg/kg s.c.) and (-)-scopolamine (1.9 mg/kg s.c.) but not by atropine methyl nitrate (2.11 mg/kg s.c.), which does not readily cross the blood-brain barrier. However, atropine methyl nitrate did prevent salivation induced by oxotremorine in the presence of THC. No synergism was detected between THC and neostigmine (0.047 mg/kg s.c.). Atropine and (-)-scopolamine also decreased the ability of chlordiazepoxide (10 mg/kg s.c.) to enhance the effect of THC on descent latency. The interaction was not antagonized by atropine methyl nitrate or mecamylamine (1.17 or 2.34 mg/kg s.c.). These results point to an involvement of central acetylcholine-releasing pathways in the cataleptic response of mice to THC.

Poster: Psychedelics Summit Cannabis: 50th Anniverary Albert Hofmann's Bicycle Ride April 18, 1993. (for conference in Santa Cruz 4-16-93 and San Francisco 4-17-93.)

POTVIN, RAYMOND H; LEE, CHE FU
Multistage Path Models of Adolescent Alcohol and Drug Use: Age Variations
Journal of Studies on Alcohol; 1980, 41, 5, May, 531-542.
Conformity-commitment, which affected drinking & drug use in a sample of 1,121 United States teenagers interviewed in 1975, was found to be influenced in 13- & 14-year-olds by parents & religion, in 15- & 16-year-olds by peers & religion, & in 17- & 18-year-olds by parents, peers, & religion. Religiousness also affected alcohol use directly among all 3 age groups & cannabis use among 15- & 16-year-olds & 17- & 18-year-olds.

PRADHAN, S N; GUHA, DEBJANI
Studies on gross behavior and electrical activity of the brain during various environmental and pharmacological states.
Research Communications in Psychology, Psychiatry and Behavior; 1976 Vol 1(2) 257-268
Recorded several electrical parameters (EEG, electrogenesis, alpha activity, and auditory evoked response) and head movements in the same cats under different physiological and pharmacological states. A state of drowsiness and CNS depressant drugs such as pentobarbital, Delta9-tetrahydrocannabinol, and mescaline decreased head movement and caused synchronization of EEG and increase in alpha activity, electrogenesis, and amplitude and area of the waves of auditory evoked response. A state of excitement or distraction and CNS stimulant drugs like LSD showed opposite effects. Nicotine at low doses (12.5 mug/kg) produced biphasic effects, showing manifestations of stimulation and then of depression; higher doses (25 mug/kg) also produced depression. Further pharmacological analysis of nicotine effects showed that cholinergic stimulation was involved at the early phase of its action and noradrenergic stimulation at the later phase. It is suggested that such behavioral and electrical activities are concomitantly modulated by some common central structures such as reticular activating system and are influenced by more than one central neurotransmitters. Different physiological and pharmacological states may produce changes in these parameters by acting on the modulatory structures and producing imbalance of the multitransmitters systems.

PROSS SH; KLEIN TW; NEWTON CA; SMITH J; WIDEN R; FRIEDMAN H
Differential suppression of T-cell subpopulations by thc (delta-9-tetrahydrocannabinol).
Int J Immunopharmacol. 1990; 12(5): 539-44
THC (delta-9-tetrahydrocannabinol), the major psychoactive component of marijuana, has been shown to suppress various immune functions in vivo and in vitro. THC suppresses murine T-lymphocyte proliferation; however, the effects on T-cell subsets remain unclear. We have stimulated cultured murine splenocytes with the mitogens concanavalin A (Con A) or phytohemagglutinin (PHA) while exposing them to varying concentrations of THC. After three days, the cells were analyzed by the fluorescent activated cell sorter for the following T-cell markers--Thy1, L3T4 and Ly2. The Ly2 cells represent the suppressor/effector T-cells while L3T4 cells represent the helper T-cell subpopulations. The results show that the dose response suppressive effect of THC on T-cell proliferation reflects a preferential inhibition of Ly2 vs L3T4 cells. The effects of THC on other functional parameters are in the process of investigation.

Queipo, D; Alvarez, F J; Velasco, A
Drug consumption among university students in Spain.
British Journal of Addiction; 1988 Jan Vol 83(1) 91-98
Examined drug consumption in 1984 among 2,921 students in a Spanish university. Cannabis was the most frequently consumed drug, followed by nonmedical consumption of amphetamines and tranquilizers. Drug consumption tends to be more frequent among males, among Ss who share a flat with friends, and among those in disagreement with their parental upbringing. Most Ss started the consumption of different drugs between the ages of 17 and 20 yrs. Curiosity, search for pleasure and happiness, and new sensations were the principal reasons for drug consumption, except for amphetamines and tranquilizers which were principally consumed as a 'study aid.'

RALPH METZNER & THOMAS PINKSON: Metzner: Hallucinogens & Ecological Consciousness
Pinkson: Purification, Death, and Rebirth; The Use of Entheogens Within a Shamanic Context
(1)Video-V277-91,

TOD MIKURIYA: The History and Medicinal Uses of Cannabis Author of The History and Medicinal Uses of Cannabis
(1)Audio-A806-91,

RATLIFFE, BRUCE E; HELISTEN, CARMEN
Street drug analysis as an adjunct to emergency medical care at rock concerts.
PharmChem Newsletter; 1974 Vol 3(7) 1,
Describes the process and results of drug analysis as an adjunct to emergency medical services at a weekend rock concert in California in the summer of 1974. Results of analyzing 46 drug samples show that nearly all tetrahydrocannabinol, mescaline, and psilocybin samples contained LSD and/or parachlorophenylalanine; that marihuana was nearly always pure; and that LSD dosages were well below those advertised in selling.

REGGIO PH; SELTZMAN HH; COMPTON DR; PRESCOTT WR JR; MARTIN BR
Investigation of the role of the phenolic hydroxyl in cannabinoid activity.
Mol Pharmacol. 1990 Dec; 38(6): 854-62
Structure-activity relationship studies have suggested that the phenolic hydroxyl group is essential for the pharmacological activity of the cannabinoids. However, it remains to be established whether it is the hydrogen of the phenolic hydroxyl that is important (possibly because this hydrogen can participate in a hydrogen bonding interaction) or whether it is the oxygen of the phenolic hydroxyl that is important (possibly because one of the lone pairs of electrons in this oxygen can serve as a hydrogen bond acceptor). Two new etherified cannabinoids were prepared in which the phenolic hydroxyl oxygen is incorporated into a fourth ring. These new compounds were designed to test the importance both of the phenolic hydroxyl oxygen and of the orientation of its lone pairs of electrons for cannabinoid pharmacological activity. O,2-Propano-delta 8-tetrahydrocannabinol (0,2-Propano-delta 8-THC) was designed to mimic delta 9-THC in its phenol conformation I (C2-C1-O-H = 7 degrees). O,10-Methano-delta 9-tetrahydro-cannabinol (0,10-Methano-delta 9-THC) was designed to mimic delta 9-THC in its phenol conformation II (C2-C1-O-H = 167 degrees). Molecular mechanics calculations revealed that 1) there are two accessible minimum energy conformers for O,2-propano-delta 8-THC, which differ principally in the conformation of the new fourth ring, and 2) there are three accessible minimum energy conformers for O,10-methano-delta 9-THC, the first two of which differ mainly in the conformation of the new fourth ring, whereas the third possesses an alternate pyran ring conformation. Wave functions and molecular electrostatic potential (MEP) maps were calculated for each accessible conformer of O,2-propano-delta 8-THC and of O,10-methano-delta 9-THC. The resultant MEP maps compared well with the corresponding MEP maps generated for delta 9-THC in each of its two minimum energy conformations (two phenolic hydroxyl positions). These results imply that 1) O,2-propano-delta 8-THC should be capable of being recognized at a site that would recognize delta 9-THC in its phenol conformation 1 and 2) O,10-methano-delta 9-THC should be capable of being recognized at a site that would recognize delta 9-THC in its phenol conformation II. Pharmacological evaluation of the analogs revealed that O,10-methano-delta 9-THC was inactive in all mouse tests, as well as the rat drug discrimination model. O,2-Propano-delta 8-THC was similar to delta 8-THC in that it depressed rectal temperature and produced antinociception and ring immobility in mice. ...

RETTORI V; AGUILA MC; GIMENO MF; FRANCHI AM; MCCANN SM
In vitro effect of delta 9-tetrahydrocannabinol to stimulate somatostatin release and block that of luteinizing hormone-releasing hormone by suppression of the release of prostaglandin E2.
Proc Natl Acad Sci U S A. 1990 Dec; 87(24): 10063-6
Previous in vivo studies have shown that delta 9-tetrahydrocannabinol (THC), the principal active ingredient in marijuana, can suppress both luteinizing hormone (LH) and growth hormone (GH) secretion after its injection into the third ventricle of conscious male rats. The present studies were designed to determine the mechanism of these effects. Various doses of THC were incubated with either stalk median eminence fragments (MEs) or mediobasal hypothalamic (MBH) fragments in vitro. Although THC (10 nM) did not alter basal release of LH-releasing hormone (LHRH) from MEs in vitro, it completely blocked the stimulatory action of dopamine or norepinephrine on LHRH release. The effective doses to block LHRH release were associated with a blockade of synthesis and release of prostaglandin E2 (PGE2) from MBH in vitro. In contrast to the suppressive effect of THC on LHRH release, somatostatin release from MEs was enhanced in a dose-related manner with a minimal effective dose of 1 nM. Since PGE2 suppresses somatostatin release, this enhancement may also be related to the suppressive effect of THC on PGE2 synthesis and release. We speculate that these actions are mediated by the recently discovered THC receptors in the tissue. The results indicate that the suppressive effect of THC on LH release is mediated by a blockade of LHRH release, whereas the suppressive effect of the compound on growth hormone release is mediated, at least in part, by a stimulation of somatostatin release.

REVUELTA, A V; ET AL
Reduction of hippocampal acetylcholine turnover in rats treated with (--)-D8-tetrahydrocannabinol and its 1',2'-dimethyl-heptyl homolog.
Brain Research; 1980 Aug Vol 195(2) 445-452
Behavioral and pharmacological studies in rhesus monkeys have shown that the levo-isomers of delta-8- and delta-9-tetrahydrocannabinol (THC) are active whereas the dextro-isomers are not active. The present study compared the effects of levo-delta-8-THC, dextro-delta-8-THC, and the dimethyl-heptyl (DMH) homolog of levo-delta-8-THC on the turnover rate of acetylcholine in various brain areas of male Sprague-Dawley rats. Results show that levo-delta-8-DMH, levo-delta-9-THC and levo-delta-8-THC all specifically reduce the turnover rate of acetylcholine in the hippocampus in a dose-dependent manner without altering the acetylcholine or choline content (except for high doses of delta-8-DMH). The selectivity of action suggests that the tetrahydrocannabinoids may activate specific transmitter receptors that indirectly modulate the activity of the cholinergic neurons in the septal-hippocampal pathway. The inhibition of hippocampal cholinergic mechanisms may play a role in the psychotomimetic activity of delta-9-THC.

Rubin, ed.
Cannabis and Culture.
Reviews in Anthropology 4(3):237-250. ()

RUPNIAK NM; SAMSON NA; STEVENTON MJ; IVERSEN SD
Induction of cognitive impairment by scopolamine and noncholinergic agents in rhesus monkeys.
Life Sci. 1991; 48(9): 893-9
In primates, treatment with scopolamine impairs performance of a spatial delayed response task in a way which mimics deficits seen spontaneously in aged primates and demented patients. Despite their efficacy in reversing scopolamine induced disruption, the effects of cholinergic agonists on cognition in aged primates and dements are unimpressive, suggesting that other neurotransmitter systems are also involved in this type of deficit. We have induced a scopolamine-like impairment of spatial delayed response performance in rhesus monkeys using phencyclidine (0.1-0.2 mg/kg i.m.), lorazepam (0.4-0.6 mg/kg s.c.) or tetrahydrocannabinol (1-4 mg/kg p.o.), but not amphetamine (0.1-0.4 mg/kg i.m.), yohimbine (0.1-1.0 mg/kg i.m.) or morphine (2-4 mg/kg i.m.). Our findings suggest that disruption of specific neurotransmitter systems other than acetylcholine may contribute importantly to cognitive decline in aging and dementia.

SACKS N; HUTCHESON JR JR; WATTS JM; WEBB RE
Case report: the effect of tetrahydrocannabinol on food intake during chemotherapy.
J Am Coll Nutr. 1990 Dec; 9(6): 630-2
[NO ABSTRACT] THC chemotherapy

SATINDER, K PAUL; BLACK, ALEXANDER
Cannabis Use and Sensation-Seeking Orientation
Journal of Psychology; 1983, 116, 1, Jan, 101-105.
Cannabis use & its relationship to sensation-seeking orientation were investigated among 24 user & 24 nonuser college & University students matched for age, sex, & education. Respondents completed a personal information questionnaire & Form V of the Sensation Seeking Scale (SSS) (Zucherman, M., Kolin, E. A., Price, L., & Zoob, I., 'Development of a Sensation-Seeking Scale,' Journal of Consulting Psychology, 1964, 28, 477-482). Users scored higher on all 4 subscales of the SSS. Analysis of covariance controlling for alcohol, cigarette, & LSD use decreased the level of total score significance between groups, but differences between users & nonusers remained significant on the disinhibition subscale & total SSS scores.

SCHERER, SHAWN E
Hard and soft hallucinogenic drug users: Their drug taking patterns and objectives.
International Journal of the Addictions; 1973 Vol. 8(5) 755-766
Compared the hallucinogenic drug-use patterns and objectives of undergraduate hard (e.g., LSD or amphetamines) and soft (marihuana or hashish) drug users with nonusers. 43 male and 37 female 18-27 yr old undergraduates completed a questionnaire to classify them into non-, soft-, and hard-drug users: 36 Ss were classified as nonusers, 28 as soft-drug users, and 16 as hard users. 37.5% of the hard users had used drugs before entering college vs 4% of the soft users. 43% of the hard users reported using drugs because their friends did, vs only 21% of the soft users. Drug users rated themselves as experiencing more social pressure to use drugs than nonusers and were almost completely in favor of the legalization of marihuana and hashish. Hard users reported greater frequencies of cannabis use than soft users, who reported a wide frequency range in their reported cannabis use. Data on parental relationships, concurrent alcohol use, and perceived dangers of drugs are also presented.

SCHOENFELD, RONALD I
Lysergic acid diethylamide- and mescaline-induced attenuation of the effect of punishment in the rat.
Science; 1976 May Vol 192(4241) 801-803
At a dose as low as 1 mcg/kg, LSD significantly decreased the suppressive effect of electric shock on licking behavior in male albino Sprague-Dawley rats. Attenuation of punishment was also obtained with mescaline, but neither dimethyltryptamine nor Delta9-tetrahydrocannabinol was active in this test. Cyproheptadine and alpha-propyldopacetamide, drugs that interfere with the function of neurons that contain serotonin, had a behavioral effect similar to that of LSD and mescaline, which suggests that the attenuation of punishment produced by these hallucinogens may result from decreased activity of such neurons.

Seligman P
A brief family intervention with an adolescent referred for drug taking.
J.ADOLESC; 1986 Sep; 9(3); P 231-42
This paper is a description of three family sessions with parents and their 19 year old and 17 year old sons. Their GP had referred the older son to the Family Institute, Cardiff as an 'urgent' case saying that the son was taking LSD and cannabis and spending periods of time away from home. The paper argues in favour of a 'non-pathological' approach to some adolescents who are on the brink of receiving serious psychiatric labels.

Seligman, Philippa
A brief family intervention with an adolescent referred for drug taking. Special Issue: Family therapy and systems work with adolescents.
Journal of Adolescence; 1986 Sep Vol 9(3) 231-242
Describes 3 family sessions with parents and their 19- and 17-yr-old sons. Their general practitioner had referred the older son to a family institute as an 'urgent' case saying that the son was taking LSD and cannabis and spending periods of time away from home. The paper argues in favor of a 'nonpathological' approach to some adolescents who are on the brink of receiving serious psychiatric labels.

SELIGMAN, PHILIPPA
A Brief Family Intervention with an Adolescent Referred for Drug Taking
Journal of Adolescence; 1986, 9, 3, Sept, 231-242.
A detailed description is offered of brief systemic work with a 19-year-old male referred by the family physician to The Family Institute (Cardiff, Wales). The boy was said to be using LSD & cannabis & spending periods of time missing from home. A nonpathological approach was taken in 3 sessions & a follow-up with the boy & his family. The therapist's method of eliciting information is described; a systemic framework was used to shift from the presenting symptom & explore & change patterns in the family relationships that created a context for the troubling behavior. The brief, problem-solving systemic approach was successful; it is suggested as a useful model in similar cases with adolescents.

SENAY EC
Drug abuse and public health. A global perspective.
Drug Saf. 1991; 6 Suppl 1: 1-65
During the past 20 years there has been a substantial increase in the data available on the prevalence and consequences of the use of drugs which are liable to abuse. The body of data is sufficiently scientific, comprehensive and global in scope to enable an overall profile of the use patterns of these drugs to be drawn in this review. The studies evaluated include those which surveyed populations of hundreds, thousands, or even more, covering a range of common drugs of abuse and using specified research methods. The data are summarised for North America, Europe, Asia and the West Pacific, Africa and South America. A complex picture has emerged, confounded by an array of factors, which this review does not address in detail, such as youth alienation, the changing role of women and the increasing sophistication of criminal networks. From a global perspective, the evidence reviewed from the various regions indicates that the use of drugs with liability for abuse is widespread and associated with public health and social problems of great magnitude. The major set of problems appears to be related to primary pattern drugs such as alcohol, nicotine, cannabis and the opioids. Cocaine may also be a worldwide threat in view of the problems it has created in some regions. Drug abuse usually starts in adolescence, and both sexes now appear to be involved where in the recent past it was predominantly men who were affected. The concurrent use of multiple substances is now becoming the modal pattern, and drug-related problems correlate with one another and with somatic, psychiatric and social pathology. Opioid use now tends to be via intravenous administration, and the doses of cannabis and cocaine base which are used are increasing. Substances with therapeutic effects on DSM-III-R diagnosable disorders, such as antidepressants and benzodiazepines, require careful consideration by policymakers because the risk:benefit ratio is different to that of primary-pattern intoxicants, especially taking into consideration the broad and proven therapeutic use of these substances and the need for their availability for patients and physicians. In conclusion, the data presented in this review indicate that the scientific description of trends and consequences of drug abuse is an indispensable first step in rational policy making. The review also identifies areas for further study and research.

Sharma, G. K.
Ethnobotany and Its Significance for Cannabis Studies in the Himalayas.
Journal of Psychedelic Drugs 9(4):337-339. (1977)

SHULGIN AT.
Hallucinogens, CNS stimulants, and cannabis.
In:S. J. Mule/*' and H. Brill [eds.]: Chemical and biological aspects of drug dependence. CRC Press, Cleveland, Ohio. Pp. 163-175. 67 (1972.)

SHULGIN AT.
Recent developments in cannabis chemistry.
J. Psyched. Drugs 2: 15-29. 58 (1969.)

SHULGIN AT
Hallucinogens, CNS stimulants, and cannabis.
In:S. J. Mule/*' and H. Brill [eds.]: Chemical and biological aspects of drug dependence. CRC Press, Cleveland, Ohio. Pp. 163-175. (1972) [#67]
[No Abstract]

SHULGIN AT
Recent developments in cannabis chemistry.
J. Psyched. Drugs 2: 15-29. (1969) [#58]
[No Abstract]

SIEGEL, RONALD K
Hallucinations.
Scientific American; 1977 Oct Vol 237(4) 132-140
Describes aspects of drug-induced hallucinations, some of which appear to be universal and similar to hallucinations accompanying migraine attacks. In a series of experiments, Ss placed in light-proof and sound-proof chambers were given either a placebo or drug, and reported, using ordinary language or special code, on the nature of their hallucinations. Images associated with placebos, dextroamphetamine, and phenobarbitol were described as black-and-white, randomly moving amorphous forms. The hallucinogens tetrahydrocannabinol, psilocybin, LSD, and mescaline produced images that were less random and more geometric, with blue hues and organized, pulsating movement. Subsequently, most forms were lattice-tunnels, movement became more organized, and colors shifted to red, orange, and yellow. Still later, complex images were reported, including childhood memories and scenes associated with strong emotional experiences. Several explanations are briefly discussed.

SILVA, M TERESA; CALIL, HELENA M
Screening hallucinogenic drugs: Systematic study of three behavioral tests.
Psychopharmacologia; 1975 Vol 42(2) 163-171
Studied the effects of several hallucinogenic and nonhallucinogenic drugs on 3 behavioral tests proposed as useful indexes of hallucinogenic activity: head twitching in mice, defecation in an open field, and suppression of responding on a differential reinforcement of low rates (DRL) schedule of reinforcement. According to the original propositions, after administration of hallucinogenic agents the frequency of head twitches would increase in 682 male albino mice; the defecation of 720 male Wistar albino rats in an open field would decrease without consistent change in ambulation, rearing and grooming; and the responding of 5 rats on a DRL schedule would yield a typical cumulative record pattern. It was found that the head twitch test was sensitive to mescaline and LSD-25 but not to D9-tetrahydrocannabinol or to myristicin and elemicin. Data suggest there is a high degree of subjectivity involved in assessing this response. In the open-field test, nonhallucinogenic drugs such as chlorpromazine and apomorphine fell into the hallucinogenic pattern proposed. In addition, the postinjection interval selected seemed to critically affect defecation scores. The DRL 'hallucinogenic' pattern occurred nonspecifically after administration of hallucinogenic and nonhallucinogenic drugs. It is concluded that the 3 tests have limited value for screening purposes.

SMART RG; ADLAF EM
Trends in treatment admissions for cocaine and other drug abusers.
Can J Psychiatry. 1990 Oct; 35(7): 621-3
This paper examines the proportion of drug abusers who report cocaine abuse as their primary problem at a Toronto clinic. In addition, characteristics of cocaine abusers are compared with those of alcohol and cannabis abusers. There is a significant increase in the proportion of drug abusers seeking treatment for cocaine use relative to other drugs, and a dramatic increase in their absolute numbers. Differences in age, marital status and socioeconomic status among cocaine, alcohol, and cannabis abusers are also noted.

SMART RG; OGBORNE AC; NEWTON TAYLOR B
Drug abuse and alcohol problems among cocaine abusers in an assessment/referral service.
Br J Addict. 1990 Dec; 85(12): 1595-8
This paper reports the social, demographic and drug abuse backgrounds of cocaine abusers seen at an alcohol and drug abuse assessment centre in Kitchener, Ontario. It compares cocaine abusers to cannabis users and alcoholics of the same age at the same centre. Cocaine and cannabis abusers are mainly young, single males while alcohol abusers are much older. The cocaine and cannabis abusers are both heavy drinkers but the cocaine group contained more high-risk drinkers, more drug injectors and had a higher alcohol consumption. Cocaine abusers are young poly-drug users for whom drinking is also a major problem. Treatment plans should take these problems into account.

SMART, REGINALD G; AND OTHERS
Preliminary Report of Alcohol and Other Drug Use among Ontario Students in 1983, and Trends since 1977.
American Mental Health Counselors Association Journal; v2 n1 p38-45 Jan 1980
Since 1977, alcohol and drug use among Ontario students has been studied every 2 years. To examine the patterns of alcohol and other drug use among Ontario students in 1983, a randomized sample of 5,835 students, representing grades 5, 7, 9, 11, and 13, from four geographical regions, completed an anonymous questionnaire. An analysis of the results showed that, as in previous surveys, the most prevalently used drug was alcohol, followed by tobacco and cannabis (such as marihuana). Most types of drugs, except for glue and other solvents, were more popular among older students (except grade 13). Also, illicit drug use, with the exception of cannabis, was still relatively infrequent among users. Only non-medical stimulant use increased between the two periods. The 1983 survey, in contrast to 1981, indicated that a slightly greater number of substances were more commonly used among males than females. This reflected significant increases in the use of six substances among males (glue, other solvents, medical barbiturates and tranquillizers, non-medical stimulants, and hallucinogens other than LSD or PCP). In contrast, no increase in drug use was found among females. (More specific drug use patterns by age, sex, grade, and geographic regions are also described in this report. Changes in usage patterns between 1981 and 1983 are analyzed, and trends in use since 1977 and 1979 are presented.) (Author/BL)

SMITH JB
Situational specificity of tolerance to decreased operant responding by morphine and l-nantradol.
Psychopharmacology Berl. 1991; 103(1): 115-20
In one experiment, key pressing of rats was maintained under a fixed-ratio schedule of food presentation in a first daily session in one environmental situation, and interruption of a photobeam was maintained under a continuous shock avoidance schedule in a second daily session in another environmental situation. After receiving acute injections of the cannabinoid l-nantradol (0.01-0.3 mg/kg), rats received daily administration of a rate-decreasing dose of the drug after the second session, then before the second session, and then before the first session. Tolerance that developed to decreased avoidance responding in the second daily session did not extend to decreased fixed-ratio responding in the first daily session, but was specific to circumstances coinciding with the pharmacological actions of l-nantradol. In a second experiment lever pressing of squirrel monkeys was maintained under an identical fixed-interval schedule of food delivery in two separate daily sessions in different experimental situations. After receiving once-weekly acute injections of morphine (0.3-3.0 mg/kg), monkeys received daily administration of a rate-decreasing dose of morphine in a counter-balanced order before each session. Just as for experiment 1, tolerance that developed in the environment coinciding with the pharmacological actions of morphine did not immediately generalize to operants in the other environmental situation. Instead, tolerance depended on both pharmacologic action as well as concurrently operating behavioral processes.

SOLOMONS K; NEPPE VM; KUYL JM
Toxic cannabis psychosis is a valid entity.
S Afr Med J. 1990 Oct 20; 78(8): 476-81
One hundred black men admitted to hospital with acute psychiatric symptoms were investigated for the presence of urinary cannabis metabolites in order to delineate the psychiatric role played by 'dagga', the potent South African cannabinol, in the study population and to determine the diagnostic value of the entity 'toxic psychosis (dagga)'. Cannabinoids were present in 29% of patients, and 31% were discharged with a diagnosis of toxic psychosis (dagga). Clinical and demographic material was gathered for all patients and no consistent differences were found between dagga-positive and dagga-negative patients or toxic dagga psychotic patients and 'functional' psychotics other than a history of recent dagga use and the dagga screening test result. The latter measure was found to be both more sensitive and more specific than the history of dagga use alone. The findings support the routine use of a simple screening test for dagga in the sample population studied. The study demonstrated the heterogeneous nature of the toxic dagga psychosis syndrome by documenting a variety of different clinical presentations, which included schizophrenia (42%), paranoia (26%), maniform psychosis (16%) and organic psychosis (16%).

SPECTER S; LANCZ G; WESTRICH G; FRIEDMAN H
Delta-9-tetrahydrocannabinol augments murine retroviral induced immunosuppression and infection.
Int J Immunopharmacol. 1991; 13(4): 411-7
Delta-9-tetrahydrocannabinol (THC), the major psychoactive component in marijuana, and the murine retrovirus, Friend leukemia virus (FLV), have been demonstrated to depress cellular immune function, including lymphocyte blastogenic transformation and natural killer cell activity. The present study demonstrates tht the two agents can work in concert to depress these immune activities more severely than either agent administered by itself. When 7.5-10 micrograms/ml THC was added in vitro to spleen cells from mice infected 2-4 weeks earlier with FLV there was a noticeable decrease, beyond that seen with the drug or virus alone, for both lymphocyte blastogenesis and natural killer cell cytotoxicity. In addition, when both FLV and THC were administered to mice concurrently with infection by herpes simplex virus (HSV), mortality attributed to the retrovirus infection occurred significantly more rapidly than in the absence of the drug and HSV. The data indicate that THC acted in the presence of a HSV infection to enhance the FLV induced mortality. By extrapolation to the human condition, these results suggest that marijuana could serve as a cofactor, possibly in conjunction with opportunistic pathogens, in the progression of infection due to the human immunodeficiency virus from latency to overt acquired immunodeficiency syndrome.

SPILLE, DIETER; GUSKI, RAINIER
(Long term use of drugs and personality characteristics: An empirical investigation.)
Zeitschrift fur Sozialpsychologie; 1975 Vol 6(1) 31-42
Studied the personality characteristics of 128 drug users (64 used cannabis and 64 used cannabis plus hallucinogens) and of 92 nonusers. Nervousness, aggressiveness, depression, and frankness were associated with drug use as measured by the Freiburger Personality Inventory (FPI). Multivariate analyses of the association between specified data of drug use, age, sex, and education with FPI variables showed differential relations: long term use of cannabis and low education were associated with depression and nervousness; use of mescal was associated with older Ss and with lower sociability, emotional lability, and depression; use of LSD was associated similar shorter duration of use and higher emotional lability. While causal relationships cannot be definitely established from cross-sectional data, results suggest that certain personality traits favor long term use of drugs.

STANDEFER JC; BACKER RC
Drug screening with EMIT reagents: a quantitative approach to quality control.
Clin Chem. 1991 May; 37(5): 733-8
We investigated the precision, linearity, accuracy, and stability of quantitative results for five drugs of abuse [amphetamines, benzoylecgonine, opiates, phencyclidine, and the cannabinoid-tetrahydrocannabinol (THC)-9-acid metabolite], analyzed in control specimens by using EMIT d.a.u. reagents (Syva Co.) with a Monarch 2000 analyzer with a nonlinear interpolation curve-fitting algorithm. The within-day and between-days coefficients of variation (CVs) were less than 5% for all drugs except THC-9-acid, which had a CV between 10% and 20%. The drift of control values during a 30-day stability study was less than 10% from target values for three weeks after a single calibration, except for THC-9-acid control values, which were stable for only two to three days. Daily calibration reduced the drift away from target values during the 30-day stability study and produced optimum precision of all drug assays. Mean control values near the National Institute on Drug Abuse cutoff limits were within 10% of their target values.

STEGER RW; MURPHY LL; BARTKE A; SMITH MS
Effects of psychoactive and nonpsychoactive cannabinoids on the hypothalamic-pituitary axis of the adult male rat.
Pharmacol Biochem Behav. 1990 Oct; 37(2): 299-302
The acute dose-response effects of delta-9-tetrahydrocannabinol (THC), cannabinol (CBN) and cannabidiol (CBD) on gonadotropin and testosterone (T) secretion and on hypothalamic norepinephrine (NE) metabolism were tested in adult male rats. THC and CBN both produced an acute suppression of plasma-luteinizing hormone (LH) and T levels and median eminence NE turnover although a dose-response relationship could not be demonstrated. CBD had no significant effect on any of these parameters and none of these cannabinoids had any effect on plasma follicle-stimulating hormone levels or median eminence LH-releasing hormone (LHRH) content. Except for the highest dose of CBN, none of the in vivo cannabinoid treatments significantly altered in vitro LH secretion although there was a trend towards decreased LH secretion. These results suggest that the decrease in LH secretion in THC- or CBN-treated rats is due to reductions in NE stimulation of LHRH release rather than to changes in LHRH synthesis or pituitary LHRH response.

Stein, Judith A; Newcomb, Michael D; Bentler, P M
Personality and drug use: Reciprocal effects across four years.
Personality and Individual Differences; 1987 Vol 8(3) 419-430
Examined the reciprocal influence of personality and drug use from late adolescence to young adulthood using a structural modeling approach. Data were obtained from 193 male and 461 female Ss over an 8-yr period. Ss were in Grades 7-9 when the study began. Questionnaires assessed multiple indicators for latent constructs of alcohol, cannabis, and hard drug use and for the personality constructs of conscientiousness, extraversion, self-esteem, and social conformity. Results show that more evidence was found for an impact of early personality traits affecting later substance use than for the reverse. Particularly strong effects were noted between early social conformity and less alcohol and hard drug use in young adulthood.

The Emporor Wears No Clothes: The Authoritative Historical Record of the Cannabis Plant, Hemp Prohibition, and How Marijuana Can Still Save the World. Jack Herer, designed and edited by Chris Conrad. HEMP / Queen of the Clubs Publishing. 1990. paperback. 182 pages. $12.95. [box 2]

THOMAS BF; COMPTON DR; MARTIN BR
Characterization of the lipophilicity of natural and synthetic analogs of delta 9-tetrahydrocannabinol and its relationship to pharmacological potency.
J Pharmacol Exp Ther. 1990 Nov; 255(2): 624-30
delta 9-Tetrahydrocannabinol, the primary psychoactive constituent in marihuana, has been studied extensively for the last 20 years; however, the mechanisms responsible for cannabinoid activity in the central nervous system are not well understood. Although it is thought that lipophilicity plays an important role in the actions of cannabinoids, studies have not been conducted to determine whether a relationship exists between the lipophilicity and behavioral potency of cannabinoid analogs. Two procedures were used to obtain n-octanol/water partition coefficients (Po/w) of naturally occurring and synthetic cannabinoids: reverse-phase high-pressure liquid chromatographic estimation of Po/w and computer calculation of Po/w based on molecular structure. The Po/w value for delta 9-tetrahydrocannabinol obtained in this study, 9.44 x 10(6), is much greater than previously reported values obtained using shake-flask methodology, yet it is in agreement with the computer calculation based on molecular structure or molecular volume. The lipophilicity of the analogs determined in this study ranged from Po/w values of 3.92 x 10(2) to 1.93 x 10(11). All pharmacologically active cannabinoid compounds were extremely lipophilic (log Po/w values greater than 4.5). Several structural alterations were found to exert considerable influence on the lipophilicity of cannabinoid analogs. Increasing the length of the side chain in a homologous series of analogs results in an increase in lipophilicity of approximately 3-fold for each CH2 group added. Introduction of a single hydroxyl group decreased lipophilicity 3- to 40-fold, depending on the site of attachment. The behavioral potency of active analogs was not found to be correlated to lipophilicity. Therefore, data obtained in this study suggest that lipophilicity is a component, but not a primary determinant of pharmacological activity in the cannabinoids.

THOMAS BF; MARTIN BR
In vitro metabolism of (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl) phenyl]-trans-4-(3-hydroxypropyl) cyclohexanol, a synthetic bicyclic cannabinoid analog.
Drug Metab Dispos. 1990 Nov Dec; 18(6): 1046-54
The oxidative metabolism of CP-55,940 [(-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3- hydroxypropyl)cyclohexanol] was studied in mouse liver S-9 microsomal preparations. [3H]CP-55,940 was incubated in a microsomal supernatant enriched with the appropriate cofactors for cytochrome P-450 oxidative metabolism. HPLC separation of petroleum ether/diethyl ether (1:1) extracts facilitated the identification of metabolites by GC/MS after derivatization with BSTFA or [2H18]BSTFA. The mass spectral data indicated that five monohydroxylated metabolites had been formed that differed with respect to the position of hydroxylation on the 1',1'-dimethylheptyl side chain. Two additional compounds were detected whose mass spectral data suggested that these metabolites were hydroxylated at two positions on the side chain. Side chain hydroxylation is consistent with the metabolic profile of delta 9-tetrhydrocannabinol (delta 9-THC) and other cannabinoid compounds. It is possible that these side chain-hydroxylated metabolites retain activity, as is the case with similar metabolites formed from delta 9- and delta 8-THC, and thereby contribute to the pharmacological profile seen with this potent synthetic cannabimimetic agent.

TROJNIAR W; WISE RA
Facilitory effect of delta 9-tetrahydrocannabinol on hypothalamically induced feeding.
Psychopharmacology Berl. 1991; 103(2): 172-6
Six male Lewis rats were tested for the effect of delta 9-tetrahydrocannabinol (delta 9-THC) on feeding evoked by electrical stimulation of the lateral hypothalamus. Treatment with delta 9-THC (0.4 mg/kg IP) decreased frequency threshold for feeding by 20.5% (+/- 4.3), causing a leftward shift in the function relating stimulation frequency to the latency to begin eating 45-mg food pellets upon stimulation onset; there was no change in the asymptotic performance that was approached with sufficiently high stimulation frequencies. Naloxone (1 and 2 mg/kg) reduced the facilitory effect of delta 9-THC, but did so at doses that can inhibit feeding in the no-drug condition. These data are consistent with evidence implicating endogenous opioids in feeding, and suggest (but do not confirm) that the facilitation of feeding by delta 9-THC may be mediated by endogenous opioids. The facilitation of stimulation-induced feeding by doses of delta 9-THC that have been found to facilitate brain stimulation reward is consistent with evidence suggesting common elements in the brain mechanisms of these two behavioral effects of medial forebrain bundle stimulation.

Trott RJ
Diminished responsibility and the drug scene.
Br.J.Addict; 1992 Feb; 87(2); P 189-92
This article sets out the provisions of S.2 (1)-(3) of the Homicide Act 1957 and the judicial interpretations placed thereon and relates the importance of this section to the offence of murder and considers the province of the expert in regard to the Act and the difficulties encountered when experts interpret the words 'disease' and 'injury'. This is illustrated in relation to a recent Murder case where the Defendant had taken LSD and cannabis voluntarily, and deals with the question as to whether construction of the Act involves any assumption that permanent injury and non-self-induced injury are necessary ingredients to bring the defendant within provisions of S.2 (1), i.e. abnormality of mind induced by injury substantially impairing mental responsibility. Similarities are suggested between persons suffering from hallucinations, due to delirium tremens, severe concussion cases and LSD trip cases, and the question is posed as to whether it would be logical to say that temporary injury to the brain by poisoning has occurred in situations where there is a motiveless and bizarre killing following ingestion of large quantities of alcohol or drugs.

TURKANIS SA; PARTLOW LM; KARLER R
Delta-9-tetrahydrocannabinol depresses inward sodium current in mouse neuroblastoma cells.
Neuropharmacology. 1991 Jan; 30(1): 73-7
Whole-cell voltage-clamp techniques were used in order to define the effects of delta-9-tetrahydrocannabinol (THC) on the voltage-gated sodium current in neuroblastoma cells. With regard to the inward sodium current, THC decreased the peak amplitude and increased both the time to peak and tau for recovery. The reversal potential was unchanged, suggesting that channel selectivity for sodium was not altered by the drug. With regard to the outward sodium current, THC had no effect on the peak amplitude, time to peak or tau for recovery. This functional alteration of the voltage-gated sodium channel may contribute to the depressant effects of the cannabinoid.

UNITED NATIONS
Decision 2 (XXXIV): Transfer of delta-9-THC and its stereochemical variants from Schedule I to Schedule II of the Convention on Psychotropic Substances, 1971.
UN Microfiche set # E/CN.7/1991/26, page 98.
At its 1045th meeting, on April 29,1991, the Commission on Narcotic Drugs, in accordance with article 2, paragraphs 5 and 6, of the Convention on Psychotropic Substances, 1971, decided that delta-9-tetrahydrocannabinol (also referred to as delta-9-THC) and its stereochemical variants should be transferred from Schedule I to Schedule II of that Convention.

WATANABE K; HIRAHASHI N; NARIMATSU S; YAMAMOTO I; YOSHIMURA H
Mouse hepatic microsomal enzyme that catalyzes oxidation of 11-oxo-delta 8-tetrahydrocannabinol to delta 8-tetrahydrocannabinol-11-oic acid.
Drug Metab Dispos. 1991 Jan Feb; 19(1): 218-21
Mouse hepatic microsomes oxidized 11-oxo-delta 8-tetrahydrocannabinol (11-oxo-delta 8-THC, aldehyde) to delta 8-THC-11-oic-acid (carboxylic acid). The reaction required NADPH and molecular oxygen and showed an optimal pH around 7.5. The activity of NADPH-dependent carboxylic acid formation was mainly localized in microsomes. The reaction was inhibited by various inhibitors of cytochrome P-450-dependent oxidation such as SKF 525-A, alpha-naphthoflavone, and metyrapone. Disulfiram and menadione also inhibited the microsomal oxidation of the aldehyde to the carboxylic acid, but pyrazole did not inhibit the reaction. The pretreatment of mice with phenobarbital significantly increased the oxidation activity on the basis of microsomal protein, but did not affect it on the basis of cytochrome P-450 content. The mechanism for the oxidation of the aldehyde to the carboxylic acid was confirmed to be oxygenation, since oxygen-18 was incorporated into delta 8-THC-11-oic acid from molecular oxygen during the hepatic microsomal oxidation of 11-oxo-delta 8-THC.

WATANABE K; KIJIMA T; NARIMATSU S; NISHIKAMI J; YAMAMOTO I; YOSHIMURA H
Comparison of pharmacological effects of tetrahydrocannabinols and their 11-hydroxy-metabolites in mice.
Chem Pharm Bull Tokyo. 1990 Aug; 38(8): 2317-9
Pharmacological effects (catalepsy, hypothermia, pentobarbital-induced sleep prolongation, anticonvulsant and analgesic effects) of delta 8- and delta 9-tetrahydrocannabinols, and their 11-hydroxy-metabolites were evaluated and compared in mice. delta 9-Tetrahydrocannabinol and 11-hydroxy-delta 9-tetrahydrocannabinol exhibited somewhat greater effects than did delta 8-tetrahydrocannabinol and 11-hydroxy-delta 8-tetrahydrocannabinol, respectively, in all pharmacological indices tested. Greater effects of 11-hydroxy-metabolites than those of tetrahydrocannabinols were also demonstrated.

WATANABE K; NARIMATSU S; YAMAMOTO I; YOSHIMURA H
Oxygenation mechanism in conversion of aldehyde to carboxylic acid catalyzed by a cytochrome P-450 isozyme.
J Biol Chem. 1991 Feb 15; 266(5): 2709-11
The oxygenation of an aldehyde, 11-oxo-delta 8-tetrahydrocannabinol to a carboxylic acid, delta 8-tetrahydrocannabinol-11-oic acid was catalyzed by cytochrome P-450 MUT-2 purified from hepatic microsomes of male ddN mice. The oxygenation mechanism was confirmed by the incorporation of oxygen-18 from molecular oxygen into the carboxylic acid formed. An aldehyde form but not a hydrated form of 11-oxo-delta 8-tetrahydrocannabinol may be a substrate for the cytochrome P-450. The oxygenation of aldehyde catalyzed by cytochrome P-450 might be a common metabolic reaction in biological systems, and should be considered as an additional role of cytochrome P-450 in biotransformation of endogenous compounds and xenobiotics.

WEAVER ML; GAN BK; ALLEN E; BAUGH LD; LIAO FY; LIU RH; LANGNER JG; WALIA AS; COO
Correlations on radioimmunoassay, fluorescence polarization immunoassay, and enzyme immunoassay of cannabis metabolites with gas chromatography/mass spectrometry analysis of 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid in urine specimens.
Forensic Sci Int. 1991 Jan Feb; 49(1): 43-56
Results obtained from three commercial immunoassay kits, Abuscreen, TDx, and EMIT, commonly used for the initial test of urine cannabinoids (and metabolites) were correlated with the 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (9-THC-COOH) concentration as determined by GC/MS. Correlation coefficients obtained based on 26 (out of 1359 total sample population) highly relevant samples, are 0.601 and 0.438 for Abuscreen and TDx. Correlation coefficients obtained from a parallel study on a different set of 47 (out of 5070 total sample population) highly relevant specimens are 0.658 and 0.575 for Abuscreen and Emit. The immunoassay concentration levels, that correspond to the commonly used 15 ng/ml GC/MS cutoff value for 9-THC-COOH, as calculated from the regression equations are 82 ng/ml and 75 ng/ml for TDx and EMIT and 120 ng/ml and 72 ng/ml for Abuscreen manufactured at two different time periods. The difference of these calculated corresponding concentrations provides quantitative evidence of the reagent specificity differences.