Spasticity Animal studies

The cannabinoid agonist WIN 55,212-2 relieves symptoms of dystonia in mutant dystonic hamsters (Richter and Losher, 1994). Cannabidiol attenuates dystonia and torticollus in mutant rats (Consroe et al., 1988), apomorphine induced turning Table 23 Selected well controlled studies on the antiemetic effects of THC in patients on cancer chemotherapy Chang et al. (1979) Frytak et al. (1979) 22 patients on cancer chemotherapy, resistant to standard drugs 15 patients on high dose methotrexate 116...

References

Achiron, A., Miron, S., Lavie, V., Margalit, R. and Biegon, A. (2000) Dexanabinol (HU-211) effect on experimental autoimmune encephalomyelitis implications for the treatment of acute relapses of multiple sclerosis, Journal of Neuroimmunology 102(1) 26-31. Arata, S., Newton, C., Klein, T. and Friedman, H. (1992) Enhanced growth of Legionella pneumophila in tetrahydrocannabinol-treated macrophages, Proceedings of the Society for Experimental Biology and Medicine 199 65-67. Baczynsky, W. O. T. and...

Neurobehavioral and in vitro actions of cannabinoids

Despite the decades of extensive investigations and recent developments in can-nabinoid research, the identification of specific mechanisms for the actions of cannabinoids have been slow to emerge. We therefore do not attempt to provide a comprehensive account of the numerous in vivo and in vitro effects of canna-binoids but a few examples from our studies and those of others. The discovery of endocannabinoids such as anandamide and 2-arachidonyly glycerol and the widespread localization of...

Respiratory system

Smoking marijuana is believed to have several dangerous effects on the respiratory system. Like tobacco smoke, cannabis smoke contains both tar carbon monoxide and carcinogens (Gold, 1994 Nahas and Latour, 1992). Unlike cigarettes, marijuana joints do not have filters, and smokers often inhale deeply and keep the smoke in their lungs for extended time to get the full euphoric effect. Marijuana smoke has about three times more tar and five to six times more carbon monoxide than cigarette smoke...

Changes effected through cannabinoid receptors

THC at lower concentrations, and at sites distal to the lung, may affect immune cell functions by signaling through cannabinoid receptors. Cannabinoid receptors have been identified both within the brain and cells of the immune system (Figure 9.5). Two cannabinoid receptors, CBX and CB2, have been identified. The CBX has been localized to neuronal tissues (Matsuda et al., 1990) and testis (Gali gue et al., 1995), and to a lesser extent to immune cells. In contrast, the CB2 has been observed...

Conclusion

Neurophysiology research is rapidly progressing to further uncover the mode of action of marijuana and cannabinoids. At the cellular level, electrophysiological data indicate that THC and cannabinoids have complex effects and affect a wide range of neuronal properties at the pre- and postsynaptic levels. Thus, canna-binoids depress neuronal activity via inhibition of Ca2+ channels to decrease excitatory neurotransmission at glutamatergic synapses, increase the K+ IA, and may increase inhibitory...

Changes effected through alterations in membranes

At high concentrations (i.e. 10-5M or greater), THC and other cannabinoids can cause membrane perturbation and disrupt cell membranes (Figure 9.4). Physical disruption of cellular membranes may affect translational events and post-transla-tional modifications such as glycosylation, phosphorylation, and proteolytic cleavage of precursor molecules. In addition, intracellular and extracellular communication through signaling molecules may be affected. Furthermore, since THC is a highly lipophilic...

Cannabinoid receptor gene expression

The expression of CBX Cnr in the CNS has been extensively studied (Onaivi et al., 1996). The CB2 receptor gene has been detected particularly in the immune system and the expression of its transcripts found in spleen, tonsils, thymus, mast cells and blood cells. CBX and CB2 Cnrs can be co-expressed in some of the same cells, in which cannabimimetic effects can be mediated by their combination. The relative abundance of the endocannabinoids and the relatively large numbers of expressed...

Implication for the medical use of marijuana

The use of cannabis for both recreational and medicinal purposes dates back to thousands of years. In recent times, there has been an increase in calls for marijuana to be legalized for medicinal use in AIDS, cancer, multiple sclerosis and other medical conditions where patients might benefit from the biological effects of cannabis. Synthetic cannabinoids such as dronabinol, marinol and nabilone already have an established use as antiemetics in nausea and vomiting associated with cancer...

Human functional studies

In chronic marijuana users, a clinical condition, loosely described as amotiv-ational syndrome associated with apathy, reduced drive and ambition, impaired ability to carry out complex tasks, loss of initiative and effectiveness, failure to pursue long-term plans, difficulty in concentrating and decline in school and work performance has been reported (McGlothlin and West, 1968 Gold, 1989 Nahas, 1984). Although firm objective data in support of this syndrome are lacking, several data based...

Decreased resistance to infection with viruses

Guinea pigs and mice have been used extensively to document the effects of cannabinoids on resistance to infectious agents and to define elements of the immune system targeted by these compounds. Morahan et al. (1979) demonstrated that THC administered intraperitoneally to BALB c mice decreased resistance to Listeria monocytogenes or herpes simplex virus type 2 (HSV-2), pathogens infectious also in humans. Animals inoculated intravenously with Listeria exhibited a significant dose-dependent...

Prostaglandins and cannabinoids in peripheral systems

Since their discovery, the prostaglandins have been known to have important roles in the reproductive systems. This has prompted investigators looking for mechanisms to explain the effects of cannabinoids on reproduction to study a possible role for the prostaglandins (Jordan and Castracane, 1976 Ayalon et al, 1977 Dalterio et al, 1978, 1981 Rettori et al., 1990). Cannabinoids appear to modulate PG levels in male and female models where they show both stimulatory and inhibitory actions. In...

Summary

The effect of cannabinoids on short-term memory in rats performing the DNMS task is quite similar to the effects of complete hippocampal removal (1) behavioral deficits are produced at long delays (2) proactive influences between trials are no longer protected by hippocampus and (3) hippocampal neurons fail to strongly encode Sample phase information. The result of these deficits is a behavioral cascade in which the hippocampus is rarely engaged in strongly encoding information critical to the...

Marijuana Addiction Introduction

Marijuana, Cannabis sativa, is a highly complex substance which contains in excess of 400 chemical entities including A9-tetrahydrocannabinol (THC), its major psychoactive component. THC has been reported to have therapeutic potential in terms of its anti-nociceptive properties, ability to reduce intraocular pressure and bronchial constriction, and action as an anti-convulsant and antiemetic agent (Munson and Fehr, 1983 Dewey, 1986). Accumulating experimental evidence indicates, also, that...

Additional synaptic inputs to the core reward system

There are several additional neural inputs to the core reward system that may modulate drug reward by modulating DA function within the core system. GABAergic efferents from the nucleus accumbens form a feedback loop to the ventral tegmental area, and nucleus accumbens medium spiny GABAergic neurons also project to other GABAergic neurons synaptically linked to both the accumbens and ventral tegmental area (Alexander and Crutcher, 1990 Kalivas et al., 1993 Van Bockstaele and Pickel, 1995)....

Cannabinoid effects on neuronal activity in CNS reward loci

It is well established that some addictive drugs (e.g. opioids, nicotine) enhance mesoaccumbens DA reward substrates by enhancing the firing rate of the second-stage DA neurons within these reward substrates (see, e.g. Gysling and Wang, 1983 Grenhoff et al., 1986). To assess whether cannabinoids act similarly, several research groups have combined cannabinoid administration in laboratory animals with in vivo single-neuron electrophysiological recording techniques. With one exception (Gifford et...

Endogenous Cns Cannabinoid Involvement In Opioid Effects On Cns Reward Substrates

Since endogenous CNS opioid mechanisms are so clearly involved in mediating at least some cannabinoid effects on CNS reward substrates, it might logically be asked whether endogenous CNS cannabinoid systems are involved in mediating opioid effects on CNS reward substrates. There is little work addressing this possibility, but the few published studies are highly provocative to this reviewer's mind, notably the facts that morphine's rewarding properties and its ability to enhance nucleus...

Sites of cannabinoid action on CNS reward substrates

As noted above, different addictive drugs enhance reward by acting at different sites within the reward substrates of the CNS. Nicotine, ethanol, benzodiazepines, and barbiturates appear to act - transsynaptically - within somatic and dendritic regions of the second-stage DA neurons in the ventral tegmental area cocaine, amphetamines, and dissociative anesthetics appear to act primarily on the axon terminal projections of the second-stage DA neurons within the nucleus accumbens. Opiates act on...

Mechanisms of cannabinoid action on CNS reward substrates

Just as different addictive drugs act at different sites of action within the CNS to enhance reward substrates, so too do different addictive drugs enhance reward substrates by acting through different mechanisms. Amphetamines (and probably some phencyclidine-like dissociative anesthetics) act as presynaptic DA releasers, cocaine as a presynaptic DA reuptake blocker, opiates and nicotine as transsynaptic enhancers of DA neuronal firing, and other addictive drugs by yet other mechanisms (for...

Concluding Remarks And Future Directions

Faster progress has been achieved in marijuana research within the last decade than in the thousands of years that marijuana has been used in human history. For many decades, research on the molecular and neurobiological bases of the physiological and neurobehavioral effects of marijuana was hampered by the lack of specific research tools and technology. The situation started to change with the availability of molecular probes and other recombinant molecules that have led to the major advances....

Antiemetic Properties Of Clinicallyuseful Cannabinoids

During 1970s and 1980s, dopamine D2 antagonists were the mainstay of antinauseant-antiemetic agents in cancer patients receiving chemotherapy. However, they had limited clinical success. Because of anecdotal reports by young cancer patients that smoking marijuana alleviated the nausea and vomiting caused by chemotherapeutic agents, both government and industry sponsored clinical trials were initiated to test the antiemetic potential of cannabinoids. These trials began in 1975 and have continued...

The Interaction Of Cannabinoids With The Membrane Lipid Bilayer

Lawrence and Gill (Lawrence and Gill, 1975), in 1976, first demonstrated that THC at low concentrations (1 micromolar) increases the molecular disorder of the liposome. At higher concentration, the effects level off and do not increase as the molecular ratio of THC to lecithin is increased. The maximum degree of fluidization (disordering) produced by THC does not approach that required to produce anesthesia and THC has been designated a partial anesthetic. The term incomplete could also be...

Cannabinoid Receptor Activation Of Ion Channels

Activation of the CBX receptor can lead to alterations in the function of multiple ion channels (Figure 15.1). Most notable is the ability of cannabinoids to inhibit voltage dependent N- and Q-type calcium channel currents both in transfected cell lines and in cell lines that contain the native receptor (Caulfield and Brown, 1992 Mackie and Hille, 1992 Mackie et al., 1995). More recently, it was demonstrated that cannabinoid CB1 receptors can inhibit L-type Ca2+ current in cerebral arterial...

Abstract

Cannabis has been used for medical purposes for centuries. With the discovery of cannabinoid receptors, there has been an explosion of research on both natural and synthetic cannabinoids. This chapter reviews both animal and human research demonstrating the potential role of cannabinoids in motivational processes and their associated disorders (hunger, appetite, pain), psychological disorders (anxiety, depression, bipolar disorder, schizophrenia, alcohol dependence) and central nervous system...

Animal models of emesis and the established cannabinoid antiemetics

In the field of antiemetic research, as has been the case of marijuana in general, clinical research has often preceded animal experiments. From the discussion of the numerous cited clinical trials, it is clear that A9-THC and its tested synthetic analogs have demonstrated efficacy and safety as moderate antiemetics in patients receiving chemotherapy. Scant published animal studies also support the antiemetic properties of these cannabinoids (London et al., 1979 McCarthy and Borison, 1981...

Time sense after tetrahydrocannabinol administration

Marijuana intoxication is known to cause changes in the perception of time (Clark et al, 1970 Mathew and Wilson, 1996 McNair et al, 1971 Melges et al., 1970a Melges I I Placebo I I 0.15 mg min I I 0.25 mg min Figure 8.9 Plasma levels after THC infusion. Figure 8.9 Plasma levels after THC infusion. et al., 1970b Melges et al., 1971 Spielberger et al, 1970 Tinklenberg et al., 1972 Tinklenberg et al., 1976). An association between time perception and cerebellar function has been reported (Keele...

Sar Of Endocannabinoids For Cannabinoid Receptors Anandamide Amidase And The Anandamide Transporter

Cannabinoids produce a wide range of pharmacological effects, which include anticonvulsant, antiglaucoma, antiemetic, antianxiety, analgesic, and antiasthmatic activity. The structure-activity relationships of cannabinoids and anandamide analogs indicate that their pharmacological activities are significantly influenced by their chemical structures and stereochemical features. The chemical structure of anandamide can be divided into two major molecular fragments (a) a polar ethanolamido head...

Effects Of Perinatal Exposure To Cannabinoids

The major psychoactive component of marijuana, A9-THC, has been shown to cross the placenta in humans (Blackard and Tennes, 1984) and in rodents (Vardaris et al., 1976). Moreover, during pregnancy, CBX receptors have been detected in uterus (Das et al., 1995), blastocytes (Paria et al., 1995) and in fetal tissue from the earliest day studied (day 11, Buckley et al., 1998), thus exposing the developing organism to potential teratogenic effects of cannabinoids throughout gestation. Hence,...

Clinical trials with nabilone

Nabilone is a synthetic cannabinoid which was developed by the Lilly laboratories. The general structure of nabilone is similar to A9-THC as they are both dibenzopyr-ans, with a dimethyl at the position 6, and a hydroxyl at the position 1. However, nabilone differs from A9-THC as it contains a dimethylheptyl side chain (instead of pentyl) at the position 3, and a ketone (instead of methyl) in the position 9. In both animals (Razdan, 1986) and humans (Archer et al., 1986), the psychoactivity of...

Basal ganglia

Basal Ganglia

The basal ganglia (masses of grey matter located deep in the cerebral hemispheres) comprise a group of brain nuclei involved in many human movement disorders such as Huntington's disease, Parkinson's disease, Hemiballism, or Tourette's syndrome. It will be discussed extensively in this chapter. The main input structures of the basal ganglia are the striatum and the subthalamic nucleus. Both receive extensive innervation from the cortex and thalamus, project to the output nuclei of the basal...

Effect Of Cannabinoids On Phospholipid Enzymes And Arachidonic Acid Biosynthesis

A phospholipid messenger system constitutes a major function of the lipid bilayer and involves signal-mediated hydrolysis of phospholipids within the membrane. The best characterized of these systems is that originating from arachidonic acid, which is released from phospholipids following activation by a phospholipase. Psychoactive cannabinoids and some of their non-psychoactive acid metabolites also release arachidonic acid from phosphatidylcholine in a dose-related manner (Hunter et al., 1985...

Chemical dependence

Dependence to cannabinoids appears to occur in humans and develop slowly with increased risk at higher doses and frequency of use (Gold, 1994 Martin and Hubbard, 2000). Compulsive use has been reported antidotally and in survey studies (Ashton, 1999). Like other drugs of abuse, cannabinoids has been shown to stimulate release of dopamine in neuroanatomical reward centers of the brain (Gardner and Lowinson, 1991). Cannabis dependence is estimated to be about 4 of the population (Gold, 1994...

Hypothetical models of cannabinoid action on CNS reward substrates

From many of the considerations reviewed above, hypothetical models of cannab-inoid action on CNS reward substrates can be developed. One model (Gardner and Lowinson, 1991 Gardner, 1992) takes as its starting point the observations that (1) intracranial cannabinoid microinfusion into the nucleus accumbens enhances accumbens DA while cannabinoid microinjection into the ventral tegmental area does not (2) the electrochemical signature of can-nabinoid-induced enhancement of forebrain DA resembles...

Possible mechanisms for effects on brain morphology

The data we present show group differences related to age of first use of marijuana. Early users were defined as those who started before the age of 17. The effects manifest themselves in 3-dimensions. (1) Both males and females who are early users have reduced cortical gray matter (as a percentage of whole brain volume) when compared to those who started use later. Differences are greater over the frontal cortex (2) The CBF in males who are early users is significantly higher compared to other...

Effects on lymphocytes other immunocytes and cytokines

Kusher et al. (1994) assessed the effect of THC (0.005-5.0 g ml) on the synthesis of TNFa by human large granular lymphocytes (LGL) in culture. These investigators reported that THC at physiological levels down-regulated TNFa production and diminished LGL cytolytic activity against K562 tumor cells. Furthermore, it was suggested that since the NK polymorphonuclear neutrophil axis represents an important early defense against the opportunistic fungus Candida albicans, repression of this system...

Other Hormones

Less is known regarding cannabinoid effects on other hormonal systems. Several hormones involved either directly or indirectly in the regulation of metabolism, i.e., growth hormone (GH), thyroid-stimulating hormone (TSH), and insulin, are affected as a result of cannabinoid exposure. The secretion of GH by the anterior pituitary gland is regulated by two hormones from the hypothalamus, GH-releasing hormone (GHRH), which stimulates GH secretion, and somatostatin, which inhibits the release of...

Other invertebrate Cnr genes

Sequence from the Caenorhabdities elegans (C. elegans) genome share weak similarity to Cnrs (Wilson et al., 1994). Cnr binding activity has been reported in the marine cyanobacterium, Lyngbya majuscula (Sitachitta and Gerwick, 1998). Cannabinoids can inhibit the growth of pathogenic amoeboflagellate Naegleria fowleri and prevents enflagellation and encystment, but do not impair amoeboid movements of this organism (Pringle et al., 1979). Cannabinoids influence the social behavior of ants...

Cannabinoids affect encoding strength but not encoding functions

The loss of Sample firing correlates described above (Figure 23.5) confirmed an earlier report that exposure to A9-THC reduced firing of hippocampal cells during the Sample phase of DMS, but not the Nonmatch phase (Heyser et al, 1993). In terms of the behavioral cascade, this means that more trials show weak encoding (red arrow, Figure 23.4b), and consequently, LDEs and miscodes are increased. The frequency distributions of ensemble Sample phase firing rates (Hampson and Deadwyler, 2000)...

Mutated receptors and binding site models Chimeric CBICB2 receptors

The most prominent ligands used for investigating fine details of interactions with the cannabinoid receptors are CP 55,940, WIN 55212-2 and SR 141716A (Figure 21.5), because of their high affinity and especially their availability as tritiated molecules. Despite the structural difference between CBX and CB2, 3H CP 55,940 binds equally well to the two receptors and activates them with similar efficacy and potency. It was striking to find that 3H CP 55,940 also failed to discriminate any of a...

History

Historical accounts suggest that the medicinal use of cannabis was once widespread both culturally and geographically. Among other things, cannabis was appreciated for its analgesic and anesthetic actions. The Chinese pharmacopeia of 2800 B.C. describes the use of cannabis as an analgesic (Iversen, 2000). Cannabis preparations were reportedly used in 200 A.D. by the Chinese physician Hua T'o to anesthetize patients before abdominal surgery (Li, 1974). Documentations regarding the medicinal use...

Clinical trials with A9THC

A9-THC is the most extensively studied antiemetic cannabinoid. Table 13.1 summarizes the antiemetic efficacy of orally administered A9-THC against chemotherapy-induced nausea and vomiting from 15 clinical trials. In these studies, patients were undergoing treatment with a variety of chemotherapeutic agents for a plethora of tumors and haematologic malignancies. The administered doses of A9-THC were between 5-15 mg m2 and its first dose was administered 1-24 h prior to the start of chemotherapy....

Chronic effects related to marijuana use

Drug induced phenomena may be subsumed under acute effects, withdrawal, chronic residual (possibly reversible) effects and permanent effects that may be associated with morphological changes. Demarcation among these categories is clearer with certain drugs but less so with others. For example, in the case of ethyl alcohol, phenomena related to intoxication (acute effect), withdrawal (delirium tremens in extreme cases), reversible functional changes (cognitive changes including memory defects)...

Sleep

Drowsiness and sleepiness are commonly observed in the later stages of marijuana intoxication. Increased sleeping time and slow wave sleep have been recorded upon acute administration of A9-THC, the major psychoactive ingredient of marijuana (Paton and Pertwee, 1973 Pivik et al., 1972). Anandamide was shown later to increase slow-wave and REM sleep in rats at the expense of wakefulness (Murillo- Rodriguez et al., 1998), while, conversely, the CBX receptor antagonist SR141716A increased...

Human Research

There is no evidence from human studies of any structural brain damage following prolonged exposure to cannabinoids. The most recent study using sophisticated technology and measurement techniques showed that frequent but relatively short-term use of marijuana does not produce any structural brain abnormalities or global or regional changes in brain tissue volume or composition assessable by magnetic resonance imaging (MRI) (Block et al., 2000a). Existing methods of brain imaging may not be...

Introduction Marijuana and movement

The recreational and medicinal properties of the marijuana plant have been known by humankind since ancient times. Today, the plant is primarily used for its euphorogenic properties, despite its continuing illegal status. But even for the common user, one of the many physiological effects known to be induced by the active ingredients in the plant is especially striking, that is, the effects on movement. The major recognized effect of marijuana on movement is the induction of hypoactiv-ity....

Nissar A Darmani

In the last two decades, there have been considerable advances in our understanding of emetic circuits and the mechanisms by which chemotherapeutics produce emesis. Cancer chemotherapy is often accompanied by severe nausea and vomiting, which can lead to refusal or delay of treatment by patients. A number of different classes of antiemetics have been employed clinically to control chemotherapy-induced emesis. These include dopamine D2 antagonists (butyrophenones, phenothiazines), cannabinoids,...

Agonists

Although marijuana (Cannabis sativa L.) has been used since time immemorial for recreational and therapeutic purposes, it was only in 1964 that its main psychotropic constituent was identified by Mechoulam and Gaoni (1965) as A9-tetrahydro-cannabinol (A9-THC) (Figure 21.4). Many other classical cannabinoids based on the A9-THC dibenzopyran structure have subsequently been developed with the aim of improving the non-specificity and only moderate affinities (Ki 30-60nM) and efficacy of A9-THC....

Stress Hormones

The hypothalamic-pituitary-adrenal axis is the major endogenous hormonal system responsible for maintaining homeostatic balance in response to stress. Beginning in the central nervous system, corticotropin-releasing hormone (CRH), synthesized in the hypothalamic parvocellular paraventricular nuclei of the hypothalamus, regulates the release of adrenocorticotropin hormone (ACTH) from the anterior pituitary gland. ACTH release stimulates the synthesis and secretion of the adrenal glucocorticoids...

Limitations Of Human Studies On Marijuana

Marijuana has been an area of significant social and scientific interest for many years, yet many questions remain unanswered or not fully answered. In part, this is due to the inherent difficulties of human research on any illegal substance and in part it is due to special characteristics of marijuana. For example, marijuana has a very long half-life making the cause and effect less obvious, and marijuana is not a specific chemical, but rather a substance derived from the cannabis sativa plant...

Drug discrimination

In the drug discrimination paradigm (see review by Balster and Prescott, 1992), laboratory animals learn to recognize the presence of a certain drug (such as nicotine, morphine, LSD, A9-THC) and express the discrimination between the drug under investigation and a control substance (placebo) in a two choice situation, where the correct choice is rewarded. Results from numerous studies indicate that animals will learn to discriminate cannabinoids from drugs from different classes and they will...

Sex Hormones Male

Serum Testosterone Hourly Fluctuation

In the male, the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are synthesized and released from the anterior pituitary gland in response to the hypothalamic peptide releasing hormone GnRH or gonadotropin-releasing hormone. Once released, LH and FSH bind to receptors within the testes where these hormones maintain spermatogenesis and testosterone secretion. Exposure to cannabinoids can result in altered levels of LH, FSH and testosterone in the male. In human...

Pharmacological Profile Of Cannabinoids

In the absence of a behavioral or physiological response which is unique for cannabinoids, Martin and colleagues (1991) have developed a multiple in vivo assay for the evaluation of cannabimimetic effects. These procedures have been shown to be predictive of psychoactive cannabinoid activity and to highly correlate with affinity for the - predominantly central- cannabinoid CB x receptor (Abood and Martin, 1992 Compton et al., 1993 Martin et al., 1991 Razdan, 1986). The full battery includes a...

Function Of The Endocannabinoid System In The Neonate

The endocannabinoids appear to play a major role in fertility and reproductive functions, which is described elsewhere in this book (S. K. Dey, Cannabinoids and reproduction). Recent work on the medicinal aspects of marijuana have indicated that the plant may be used beneficially to combat weight loss in AIDS and cancer patients by enhancing appetite (Mechoulam et al., 1998b). More recently we have uncovered evidence that the above mentioned observations may just be the tip of the iceberg of...

Brain Damage From Head Injury Excitotoxins Ischemia Infection And Poison

A nonpsychotropic cannabinoid, HU-211, has cerebroprotective effects. HU-211 Dronabinol is a synthetic, nonpsychotropic cannabinoid, which has been shown to act as a noncompetitive N-methyl-D-aspartate NMDA receptor antagonist Shohami et al., 1993 . These authors administered HU-211 1, 2 and 3 h after closed head injury in anesthetized rats. The drug reduced blood-brain barrier breakdown and improved motor functions on beam walking and balancing tasks. Raising NMDA and glutamate levels in the...

Cannabis Markianos

E., Sauss, C., Fan, F., Tilton, C. L. and Martin, B. R. 1993 Development of behavioral tolerance to A9-THC without alteration of cannabinoid receptor binding or mRNA levels in whole brain, Pharmacology Biochemistry and Behavior 46 575-579. Adams, I. B. and Martin, B. R. 1996 Cannabis Pharmacology and toxicology in animals and humans, Addiction 91 1585-1614. Amen, D. G. and Waugh, M. 1998 High resolution brain SPECT imaging of marijuana smokers with AD HD, Journal of Psychoactive Drugs...

Antiemetic effect in cancer chemotherapy

Cannabinoids can prevent the nausea and vomiting induced by cancer chemotherapy Dewey, 1986 . Both clinical and animal studies indicate that certain cannab-inoids have therapeutic potential as antiemetic agents. Vomiting is the expulsion of contents of the gut, largely by forces generated by the respiratory muscles Levitt, 1986 . Cannabinoids can affect cerebral function, above the level of the vomiting reflex Steele, 1980 . Therefore, cannabinoids may suppress vomiting through descending...

Pyrolysis products

The phenolic cracking products of cannabidiol were isolated and tested for COX-1 inhibition Spronck et al., 1978 . Several of the products showed activity, the most potent being 2-methylolivetol which was about 12 times more potent than cannabid-iol but five times less active than indomethacin. Since cannabidiol is usually the most abundant cannabinoid in the plant, these pyrolysis products may add to the analgesic anti-inflammatory effects of smoked Cannabis. It is probably safe to assume that...

Pituitary gland

There is some evidence that cannabinoids may regulate pituitary hormone secretion by a direct action on the pituitary itself. A diffuse population of CBX cannabinoid receptors have been identified in the anterior pituitary Gonz lez et al., 1999, 2000 and the endogenous cannabinoid 2-arachidonoyl-glycerol can be quantified from rat anterior pituitary extracts Gonz lez et al, 1999 . Pituitary levels of cannabinoid receptor and endocannabinoid can be regulated by the sex steroid hormones estrogen...

Spinal cord and dorsal root ganglion

Numerous fibers labeled for CBX receptors are found in the spinal cord and are especially numerous in the dorsal horn. At least half of the binding in the dorsal horn has a presynaptic origin on dorsal root ganglion input terminals. Fibers extending from the white matter into the grey matter are observed under the central canal. Cells with a very light sheet of immunoreactivity are observed throughout the grey matter of the spinal cord. Very lightly labeled neurons and their processes are...

Entourage effect

Another phenomenon which can be observed with endocannabinoids but not with plant-derived or synthetic cannabinoids is the entourage effect Ben-Shabat et al., 1998 . Thus, 2-AG when isolated from brain as well as spleen and gut, is accompanied by several 2-acyl-glycerol esters, two major ones being 2-palmitoyl-glycerol and 2-linoleoyl-glycerol. These two esters do not bind to the cannabinoid receptors. However, they potentiate the apparent binding of 2-AG to its receptor while...

Structural features of the cannabinoid receptors

Many studies have been undertaken to determine the nature of ligand-cannabinoid receptor interactions at the molecular level. The clear objective is to arrive at more potent and more subtype specific ligands, associating therapeutic effectiveness with a minimum of undesirable psychoactive and other side-effects. Most of the past efforts have concentrated on classical structure-activity relationships to determine the cannabinoid pharmacophore using different series of classical and non-classical...