Distribution of Cannabinoid Receptors within the CNS

Results obtained in autoradiographic studies with rat brain and spinal cord indicate that the distribution pattern of specific binding sites for cannabinoids within the CNS is heterogeneous, unlike that for any other known receptor type and consistent with the known ability of cannabinoid receptor agonists to impair cognition and memory, to alter motor function and movement and to relieve pain (Herkenham et al., 1990, 1991b). The highest concentrations of cannabinoid binding sites in rat brain...

Amphetamines

It is unusual for cannabis and amphetamines to be taken together socially, since they have very different, and to some extent, opposing effects. Studies of co-administration in man, using oral dexamphetamine and smoked cannabis, tend to show that each drug exerts its characteristic effects independent of the presence of the other drug. For example, in one investigation 15mg dexamphetamine largely failed to counteract the negative effects of cannabis on tests of cognition, except for a small...

Barbiturates

Administration of both THC and cannabidiol results in inhibition of the metabolism of barbiturates in man and in experimental animals. In an investigation of the subjective effects of giving the combination, intravenous THC (27-134 g per kg body weight) was given to seven volunteers who had already received a single dose of intravenous pentobarbitone (100mg per 70kg body weight). Five of the volunteers experienced intense psychotropic side effects such as hallucinations and anxiety as a result...

Cannabinoid Receptor Antagonists

3.2.1 Cannabinoid CB1 Receptor Antagonists Two compounds have been reported to behave as competitive, surmountable CB1 receptor antagonists (Figure 8). One of these is LY320135 which has 16.5 times greater affinity for CB1 than CB2 receptors (Table 1). The pharmacology of this compound has yet to be reported in detail. The other compound is SR141716A (Rinaldi-Carmona et al., 1994). This potently displaces 3H CP 55,940 from specific binding sites, binds at least 57 times more readily to CB1 than...

Simon Wills

Head of Drug Information Service, St Mary's Hospital, Portsmouth, UK Information on the adverse effects of cannabis has accrued over the past few decades in a piecemeal fashion. Unfortunately, systematic, well-conducted research on the toxicology of the drug in humans is comparatively rare. In most cases, animal studies are of dubious relevance to human toxicology, and this review concentrates almost exclusively on investigations involving humans. Most information has come from small scale...

Ethanol

Human performance in tests of mental, motor and perceptual ability is significantly reduced when THC or cannabis is taken with ethanol before testing (Manno et al., 1971 Bird et al., 1980). This detrimental effect is greater with the combination than when either agent is taken alone. In 1992, Lukas et al. studied the interaction between alcohol and cannabis in 15 human volunteers. After consuming 0.7 g per kg body weight of ethanol, peak plasma levels of 78mg dl occurred 50 minutes later....

Inhibitors of Anandamide Biosynthesis and Hydrolysis

Several agents have been identified that inhibit the enzymic hydrolysis of anandamide to arachidonic acid and ethanolamine when administered at concentrations lying in the nM or pM range (Table 6). These are phenylmethylsulfonyl fluoride (PMSF), diisopropylfluorophosphate (DFP) and p-bromophenylacyl bromide which are general protease inhibitors, thimerosal, p-chloromercuribenzoic acid (PCMB) and p-hydroxymercuribenzoate which are sulphydryl reactive agents, arachidonyl trifluoromethyl ketone...

Cytotoxic Agents

In vitro studies using human cancer cell lines reveal that tetrahydrocannabinol does not potentiate or antagonise the cytotoxic actions of actinomycin D, adriamycin, methotrexate, cisplatin, nitrogen mustard or velban (Harbell and DiBella, 1982). The cancer cell lines used were for human breast, uterus, ovary and melanoma. By contrast, one study has suggested that tetrahydrocannabinol has additive immunosuppressant effects when administered at the same time as cyclophosphamide in rats (Ader and...

Cannabidiol

Anandamide Receptor

Figure 3 Structures of the cannabis constituents, delta-8-tetrahydrocannabinol, cannabinol and cannabidiol Figure 4 Structure of the nonclassical cannabinoid receptor agonist, CP 55, 940. The less active (+)-enantiomer of this compound is CP 56, 667 Figure 4 Structure of the nonclassical cannabinoid receptor agonist, CP 55, 940. The less active (+)-enantiomer of this compound is CP 56, 667 Many cannabinoid receptor agonists contain chiral centres and exhibit marked stereoselectivity in both...

Alcoholism

The acute and chronic toxicity profile of cannabis is described in Chapter 10 of this volume. Liver damage is not a prominent feature and it has been suggested that alcoholics might be encouraged to shift their dependence from alcohol to cannabis on grounds of increased safety, in a parallel with the substitution of methadone for heroin in addiction with the latter. There are no reports of individual cannabinoids being investigated in this respect. In spite of early reports of success in...

Theophylline

Jusko studied the effects of cannabis on the clearance of theophylline in two studies. In the first of these, fourteen cannabis smokers were recruited (Jusko et al., 1978). Cannabis users had smoked the drug at least twice weekly for several months. Seven of them smoked cannabis only, and seven smoked tobacco regularly as well. The half-life and clearance of aminophylline varied in each of the groups studied (hrs) (ml kg hr) Non-smokers (n 19) 8.1 52 Cannabis alone (n 7) 5.9 73 Tobacco alone (n...

Glaucoma

Cannabis smoking and the oral ingestion of several of its derivatives have been shown to cause an appreciable drop in intraocular pressure (Hepler and Frank, 1971 Cooler and Gregg, 1976 West and Lockhart, 1978) and it is known that patients with open angle closure glaucoma smoke cannabis for this purpose. When smoked, cannabis containing the equivalent of 20-30 mg of THC has been shown to lower intraocular pressure in an heterogeneous group of glaucoma patients (Crawford and Merritt, 1979) and...

Haffners Tail Pinch Test

An artery clip is placed on the tail of a rat and the time taken for the rat to bite at the clip measured. THC was found to be a very effective analgesic at 11 mg kg orally where as no analgesia was seen with aspirin at 300mg kg (Sofia et al., 1973). There are many reports of analgesic tests in animals using cannabis or THC and all have varying results (Mechoulam, 1986 Martin, 1985). This may be due to the species used in the experiment or even the housing conditions before and during the...

Elimination

The major excretory pathway is the biliary system about 65 of the nabilone dose is excreted in the faeces and 20 in the urine as polar, acidic metabolites. THE FUTURE FOR CANNABIS AS A DRUG FOR PAIN RELIEF Pharmacologically, cannabis is referred to as a dirty drug. It contains many active compounds that have many effects, the mechanisms of which are barely known. It is tempting to consider all these compounds a hindrance to development but they must be thought of as exciting opportunities. A...

Adenylate Cyclase and Mitogen Activated Protein Kinases

It is now well-established that cannabinoid receptor agonists can inhibit the production of cyclic AMP and the more recent observation, that these agonists can activate mitogen-activated protein (MAP) kinases, is also generally accepted (see Childers and Deadwyler, 1996 Pertwee, 1988 1997). The evidence that these effects are mediated by cannabinoid receptors and, indeed, that CB1, CB1(a) and CB 2 receptors are all coupled through G-proteins to adenylate cyclase and MAP kinases is summarized in...

Antidiabetic Drugs

Cannabis increases appetite and so when taken regularly it may appear to reduce the effectiveness of antidiabetic medication by increasing carbohydrate intake. An investigation of healthy non-diabetic adults showed that smoked cannabis had no ill effects upon carbohydrate metabolism (Permutt et al., 1976 Weil et al., 1968). Monitoring of blood glucose levels revealed no episodes of hypoglycaemia amongst seven patients who had fasted for 24-72 hours beforehand. The smoking of cannabis was also...

Effects on Anxiety and Insomnia

Cannabis smoking produces a relaxant effect which most users value and it has been suggested that the beneficial effects of cannabis and THC observed in neurological disorders such as motor tics, dystonias and Huntingdon's chorea are due to sedative and anxiolytic actions. In addition, sedation is by far the most common side effect of cannabis, and in particular THC, observed in clinical trials against a range of disorders. This has lead to the suggestion that cannabis and some cannabinoids may...

Use as an Antiemetic

Many agents used in cancer chemotherapy produce severe nausea and vomiting in most patients. Symptoms can last for hours or days and have a major impact on patient nutrition and electrolyte status, body weight and physical and mental resilience to both the disease and its treatment. The current choice of available anti-emetics is limited and most are only partially effective, which may lead patients to refuse therapy all together, or for clinicians to use chemotherapeutic regimens which are...

Steps in Pain Perception

Nociceptors (pain receptors) are present in the skin and most other tissues. They respond to mechanical, thermal or chemical stimulation. The chemical stimulation is due to a variety of substances released into damaged tissues, for example prostaglandins and bradykinin. Sensation is carried to the spinal cord either by fast fibres, which detect sharp, localised, short-lived pain, or by slow fibres, which carry signals of diffuse, ongoing pain. Wind up is a normal process in which peripheral and...

The Cannabis Plant Botany Cultivation And Processing For

Cannabis Kafiristanica

Department of Pharmacy, Kings College London, UK Cannabis plants have been cultivated in Europe, Asia, Africa and the Americas for hundreds, perhaps even thousands of years as a source of three main products hemp fibre, cannabis seeds and medicinal or narcotic preparations (Fairbairn, 1976). Hemp fibre is obtained from cannabis stems, and has been used over the centuries for the production of textiles, rope and sacking. It is strong and durable, composed of about 70 cellulose and reaches...

Benefits and Side Effects of Nabilone and Cannabis

As time has passed we have observed many patients using nabilone and or cannabis. The effects and side effects have been the same although the effects of cannabis have always been preferred. From our observations the benefits can probably be divided into 3 categories with possibly a variety of mechanisms 1. For pain directly arising from nerve damage (neuropathic) pain a direct reduction in pain was observed. Therefore effects on the receptors within the pain pathways can be proposed. 2. For...

Hypertension

Hypotension and tachycardia are well-recognised effects of cannabis and cannabinoid use in man (Benowitz and Jones, 1981). The antihypertensive effects of the cannabinoids appear to be independent of their psychotropic effects for example CBD, a non-psychotropic derivative, is active (Adams et al., 1977). There is no clinical trial evidence that cannabis or any of its derivatives would be satisfactory alternatives to established agents in the long-term control of elevated blood pressure. While...

Cannabis Use And Abuse By Man An Historical Perspective

Head of the Drug Information Service, St Mary's Hospital, Portsmouth, UK ORIGINS The hemp plant, Cannabis sativa, is native to central Asia north of the Himalayas. It was initially confined to an area stretching from Turkestan in the west, to Pakistan in the east. Southern China probably marked the northernmost boundary of this original domain. Hemp has subsequently become much more widespread, largely due to the intervention of man. Cannabis, a dioecious species, is a member of the...

Arachidonic Acid

Shivachar et al., (1996) have obtained evidence that activation of cannabinoid CB1 CB1(a) receptors can lead to the mobilization of arachidonic acid. They found delta-9-THC and anandamide (0.5-5 M) to produce increases in the level of free 3H arachidonic acid in prelabelled rat cortical astrocytes and that these increases could be attenuated by pertussis toxin and by SR141716A, albeit only at the rather high concentrations of 1 and 10 M. Results from earlier investigations indicate that...

The Chemistry Of Cannabis

Thc Compound C5h11

1 Department of Pharmacy, King's College London, UK 2 National Center for the Development of Natural Products, University of The phytochemistry of Cannabis sativa has been extensively researched and more than four hundred compounds belonging to a variety of phytochemical groups have been reported to occur in the plant. According to one estimate, over 7000 scientific papers had been published on cannabis, its constituents and their pharmacological activities by 1980 Turner et al., 1980 . Many...

Ion Channels

Experiments with various cultured cell lines have shown cannabinoid receptor agonists to inhibit N and P Q-type calcium channels and activate A-type and inwardly rectifying potassium channels Table 5 . The available data indicate these effects are mediated by CB1 receptors coupled to inhibitory G-proteins but not by CB2 receptors. In particular, a cannabinoids show concentration-dependence and appropriate stereoselectivity and potency effective at lt 1 M as modulators of inward calcium...

Fluoxetine

THC causes aggressive behaviour in rats that have been selectively deprived of REM sleep. The administration of fluoxetine or tryptophan was found to potentiate this aggression. These drugs boost CNS levels of serotonin, but drugs with anti-serotonin effects prevented THC causing aggression Carlini and Lindsey, 1982 . In 1991, Stoll and colleagues reported the case of a 21 year old woman who developed mania subsequent to taking both fluoxetine and cannabis. She had smoked cannabis on several...

Analytical And Legislative Aspects Of Cannabis

This first section of Chapter 4 is concerned with forensic definitions of cannabis and its products as a controlled drug of abuse. Three following sections address related offences and attitudes, techniques used in forensic analysis, and the pharmaceutical quality of cannabis products. 1.1 International Conventions and National Enactments The various international conventions and protocols, and the succession of 'Dangerous Drugs' legislation in the UK, are discussed in this section and...

Propranolol

This beta-blocker inhibits the cardiac acceleration caused by cannabis Beaconsfield et al, 1972 Hillard and Vieweg, 1983 Sulkowski et al., 1977 . Propranolol may also attenuate the reddening of the eyes that is so common after smoking cannabis. It would not be anticipated that propranolol would affect the ability of cannabis to impair cognition, and this was confirmed in one study Drew et al., 1972 . However, another study of six experienced cannabis smokers revealed that pre-treatment with...

Disulfiram

A single case report has described an interaction between cannabis and disulfiram Lacoursiere and Swatek, 1983 . A 28 year old man taking disulfiram 250 mg daily exhibited signs of hypomania following the smoking of cannabis. He likened this to the effects of amphetamine. He was hyperactive, euphoric and suffered from pressure of speech, irritability and insomnia. He had used cannabis prior to commencing disulfiram and had not experienced adverse reactions. Furthermore, when disulfiram was...

United States

Although the cultivation of hemp has been actively discouraged in the past, there is a growing demand for textiles and other products made from more environmentally friendly, 'biosustainable' crops than cotton or wood. With the exception of the flowers, leaves, hashish resin and fertile seed, it is legal to import raw hemp products for processing. The number of companies manufacturing hemp products from imported hemp fibre has mushroomed in the last five years so that at present, there are over...

Cbo Cannabinoid Uses

Cannabinerolic Acid Metabolism

A9-thc acid a, A9-thca A9-thc acid B, A9-thca A9-thc-c1 A9-thca-c1 A9-thcv, A9-thc-c3 A9-thcva, A9-thca-c3 A9-thc-c4 A9-thca-c4 Figure 3 Proposed biogenetic pathway for the main cannabinoids Figure 3 Proposed biogenetic pathway for the main cannabinoids products may arise either by decarboxylation of the corresponding acids during harvesting and storage Shoyama et al., 1975 or by a biosynthetic pathway analogous to that shown, but involving the equivalent neutral precursors Kajima and Piraux,...