Relation Between Effects of Cannabinoid Derivatives on the Twitch Response of the Isolated Guinea-Pig Ileum and Their Psychotropic Properties

Rosell, Sune; Björkroth, Ulla; Agurell, Stig; Leander, Kurt; Ohlsson, A; Martin, B. R.; Mechoulam, Raphael

doi:10.1016/b978-0-08-023759-6.50009-3

Cited by 4 publications

(3 citation statements)

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“…The rank order of potencies of cannabinoids for inhibition of electrically evoked contractions of guinea pig MPLM or whole ileum correlates well with that of their psychotropic potencies and of their affinities for specific CB 1 binding sites in brain tissue10 12-14 19 (see also Pertwee2). …”

Section: Cannabinoids Inhibit Electrically Evoked Contractions Of Isomentioning

confidence: 69%

Cannabinoids and the gastrointestinal tract

Pertwee

2001

Gut

288

239

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The enteric nervous system of several species, including the mouse, rat, guinea pig and humans, contains cannabinoid CB1receptors that depress gastrointestinal motility, mainly by inhibiting ongoing contractile transmitter release. Signs of this depressant effect are, in the whole organism, delayed gastric emptying and inhibition of the transit of non-absorbable markers through the small intestine and, in isolated strips of ileal tissue, inhibition of evoked acetylcholine release, peristalsis, and cholinergic and non-adrenergic non-cholinergic (NANC) contractions of longitudinal or circular smooth muscle. These are contractions evoked electrically or by agents that are thought to stimulate contractile transmitter release either in tissue taken from morphine pretreated animals (naloxone) or in unpretreated tissue (γ-aminobutyric acid and 5-hydroxytryptamine). The inhibitory effects of cannabinoid receptor agonists on gastric emptying and intestinal transit are mediated to some extent by CB1 receptors in the brain as well as by enteric CB1 receptors. Gastric acid secretion is also inhibited in response to CB1 receptor activation, although the detailed underlying mechanism has yet to be elucidated. Cannabinoid receptor agonists delay gastric emptying in humans as well as in rodents and probably also inhibit human gastric acid secretion. Cannabinoid pretreatment induces tolerance to the inhibitory effects of cannabinoid receptor agonists on gastrointestinal motility. Findings that the CB1 selective antagonist/inverse agonist SR141716A produces in vivo and in vitro signs of increased motility of rodent small intestine probably reflect the presence in the enteric nervous system of a population of CB1 receptors that are precoupled to their effector mechanisms. SR141716A has been reported not to behave in this manner in the myenteric plexus-longitudinal muscle preparation (MPLM) of human ileum unless this has first been rendered cannabinoid tolerant. Nor has it been found to induce “withdrawal” contractions in cannabinoid tolerant guinea pig ileal MPLM. Further research is required to investigate the role both of endogenous cannabinoid receptor agonists and of non-CB1 cannabinoid receptors in the gastrointestinal tract. The extent to which the effects on gastrointestinal function of cannabinoid receptor agonists or antagonists/inverse agonists can be exploited therapeutically has yet to be investigated as has the extent to which these drugs can provoke unwanted effects in the gastrointestinal tract when used for other therapeutic purposes.

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Section: Cannabinoids Inhibit Electrically Evoked Contractions Of Isomentioning

confidence: 69%

Cannabinoids and the gastrointestinal tract

Pertwee

2001

Gut

288

239

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“…The effects of cannabinoids on the vascular system appear to be mediated by altered autonomic control of both the heart and blood vessels (ADAMS et al 1976;BENOWITZ et al 1979;JANDHYALA and BUCKLEY 1977), and indeed the cannabinoids possess some anticholinergic properties which may contribute to this response (DREW and MILLER 1974;GASCON and PERES 1973;LAYMAN 1971;ROSELL et al 1976ROSELL et al , 1979. Effects on heart rate have been linked to altered parasympathetic function of the vagus nerve (BENOWITZ et al 1979;HOLLISTER 1986).…”

Section: C) Cardiovascular Mechanismsmentioning

confidence: 99%

Marihuana

Compton¹,

Harris²,

Lichtman³

et al. 1996

Pharmacological Aspects of Drug Dependence

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Among the drugs of abuse which are regulated under the United States Controlled Substances Act and the International Conventions, none has created more intense public debate and controversy than marihuana. Marihuana is one of many names given to the leaves and flowering tops of the plant Cannabis sativa. The plant grows in all temperate regions of this planet and has been used commercially as a source of fiber and oil. Wherever the plant grows people have learned to ingest the material for its introxicating effects. The usual routes of administration are by mouth or smoking. It has been estimated that, worldwide, more than one hundred million individuals are regular users of the plant material. However, accurate data on this situation are not available. In the United States, use data have been collected on a regular basis using two large surveys, the National Household Survey on Drug Abuse (SUBSTANCE ABUSE AND MENTAL HEALTH SERVICES AD-MINISTRATION 1994) and the Monitoring the Future Survey (JOHNSTON et al. 1994) which covers eighth, tenth, and twelfth grade students in public and private schools. Figure 1 presents the data over time for lifetime, annual, 30 day, and daily use of marihuana among high school seniors in the United States (JOHNSTON et al. 1994). As can be seen, use peaked from 1978 to 1980 and had been declining slowly up to 1992. From 1992 to 1993 there was a significant increase in all use categories. Even more disturbing was the fact that very similar trend data were reported for eighth and tenth graders. This was matched in 1992 and 1993 by a decrease in the reported "perceived risk" from use of the drug.Data from the Household Survey revealed similar findings among those 12-17 years old. It is estimated that in 1993, 600000 individuals in this age group used marihuana weekly. There was also an increase in reporting that "obtaining marihuana is fairly or very easy." These trends should give us early warning of increased future public health problems. This is especially true when one looks at the increasing concentrations of /1"tetrahydrocannabinol (/1"-THC), the psychoactive principal found in confiscated samples of the plant material. This is illustrated in Fig. 2. During the years of peak use in the United States (1976)(1977)(1978)(1979)(1980) the average /1l)-THC content of confiscated cannabis was about 1.5%. There was a steady increase C. R. Schuster et al. (eds.

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“…An observation which emerges from a review of all of these studies is that some cannabinoids can be structurally dissimilar as in delta-9-tetrahydrocannabinol (delta-9-THC) and Abbott 40656 (Rosell et al 1979) and yet can have similar activities; whereas others, which show only slight structural differences as in 10-alpha-OH-delta-8-THC and 10-beta-OH-delta-8-THC (Edery et al 1971). can exhibit dramatic activity differences (figure 1).…”

Section: Introductionmentioning

confidence: 99%

Molecular Determinants for Cannabinoid Activity: Refinement of a Molecular Reactivity Template

Reggio

1987

PsycEXTRA Dataset

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Relation Between Effects of Cannabinoid Derivatives on the Twitch Response of the Isolated Guinea-Pig Ileum and Their Psychotropic Properties

Cited by 4 publications

References 4 publications

Cannabinoids and the gastrointestinal tract

Cannabinoids and the gastrointestinal tract

Marihuana

Molecular Determinants for Cannabinoid Activity: Refinement of a Molecular Reactivity Template

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