Pharmacological actions of cannabinoids.

doi:10.1007/3-540-26573-2_1

Home
/
Papers
/
Pharmacological actions of cannabinoids.

Book Chapter•DOI•

Pharmacological actions of cannabinoids.

Roger G. Pertwee¹•Institutions (1)

University of Aberdeen¹

01 Jan 2005-Handbook of experimental pharmacology (Springer Berlin Heidelberg)-Vol. 168, Iss: 168, pp 1-51

TL;DR: More information is beginning to emerge about the pharmacological actions of the non-psychoactive plant cannabinoid, cannabidiol, as well as acting on CB1 and CB2 receptors, and there is convincing evidence that anandamide can activate transient receptor potential vanilloid type 1 (TRPV1) receptors.

read less

Abstract: Mammalian tissues express at least two types of cannabinoid receptor, CB1 and CB2, both G protein coupled. CB1 receptors are expressed predominantly at nerve terminals where they mediate inhibition of transmitter release. CB2 receptors

...read moreread less

Citations

PDF

Open Access

More filters

Journal Article•DOI•

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

[...]

Pal Pacher¹, Sandor Batkai¹, George Kunos¹•Institutions (1)

National Institutes of Health¹

01 Sep 2006-Pharmacological Reviews

TL;DR: A comprehensive overview on the current state of knowledge of the endocannabinoid system as a target of pharmacotherapy is provided.

...read moreread less

Abstract: The recent identification of cannabinoid receptors and their endogenous lipid ligands has triggered an exponential growth of studies exploring the endocannabinoid system and its regulatory functions in health and disease. Such studies have been greatly facilitated by the introduction of selective cannabinoid receptor antagonists and inhibitors of endocannabinoid metabolism and transport, as well as mice deficient in cannabinoid receptors or the endocannabinoid-degrading enzyme fatty acid amidohydrolase. In the past decade, the endocannabinoid system has been implicated in a growing number of physiological functions, both in the central and peripheral nervous systems and in peripheral organs. More importantly, modulating the activity of the endocannabinoid system turned out to hold therapeutic promise in a wide range of disparate diseases and pathological conditions, ranging from mood and anxiety disorders, movement disorders such as Parkinson9s and Huntington9s disease, neuropathic pain, multiple sclerosis and spinal cord injury, to cancer, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity/metabolic syndrome, and osteoporosis, to name just a few. An impediment to the development of cannabinoid medications has been the socially unacceptable psychoactive properties of plant-derived or synthetic agonists, mediated by CB 1 receptors. However, this problem does not arise when the therapeutic aim is achieved by treatment with a CB 1 receptor antagonist, such as in obesity, and may also be absent when the action of endocannabinoids is enhanced indirectly through blocking their metabolism or transport. The use of selective CB 2 receptor agonists, which lack psychoactive properties, could represent another promising avenue for certain conditions. The abuse potential of plant-derived cannabinoids may also be limited through the use of preparations with controlled composition and the careful selection of dose and route of administration. The growing number of preclinical studies and clinical trials with compounds that modulate the endocannabinoid system will probably result in novel therapeutic approaches in a number of diseases for which current treatments do not fully address the patients9 need. Here, we provide a comprehensive overview on the current state of knowledge of the endocannabinoid system as a target of pharmacotherapy.

...read moreread less

1,857 citations

Cites background from "Pharmacological actions of cannabin..."

...Surprisingly, SR141716 and the CB2 antagonist SR144528 were also reported to have antiinflammatory effects (Smith et al., 2000, 2001), which may be attributed to their inverse agonist properties or to CB1/2 receptor-independent mechanisms (reviewed in Begg et al., 2005; Pertwee, 2005b,c)....
[...]
...…marijuana and the recent resurgence of interest in its medicinal properties have been the subject of excellent reviews (Mechoulam, 1986; Iversen, 2000; Di Marzo et al., 2004; Howlett et al., 2004; Pertwee, 2005a; Piomelli, 2005; Di Marzo and Petrocellis, 2006; Mackie, 2006; Pagotto et al., 2006)....
[...]
...The reason for the opposite effects of pharmacological blockade versus genetic knockout of CB1 receptors is not clear and may be related to the CB1 receptor-independent effects of antagonists (Begg et al., 2005; Pertwee, 2005b,c)....
[...]

Journal Article•DOI•

The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin

[...]

Roger G. Pertwee¹•Institutions (1)

University of Aberdeen¹

01 Jan 2008-British Journal of Pharmacology

TL;DR: This review focuses on the manner with which three of these compounds, (−)‐trans‐Δ 9‐tetrahydrocannabinol (Δ9‐THC), (−]‐cannabidiol (CBD) and (−)-trans‐ Δ9‐TetrahYDrocannabivarin (Γ‐THCV), interact with cannabinoid CB1 and CB2 receptors.

...read moreread less

Abstract: Cannabis sativa is the source of a unique set of compounds known collectively as plant cannabinoids or phytocannabinoids. This review focuses on the manner with which three of these compounds, (-)-trans-delta9-tetrahydrocannabinol (delta9-THC), (-)-cannabidiol (CBD) and (-)-trans-delta9-tetrahydrocannabivarin (delta9-THCV), interact with cannabinoid CB1 and CB2 receptors. Delta9-THC, the main psychotropic constituent of cannabis, is a CB1 and CB2 receptor partial agonist and in line with classical pharmacology, the responses it elicits appear to be strongly influenced both by the expression level and signalling efficiency of cannabinoid receptors and by ongoing endogenous cannabinoid release. CBD displays unexpectedly high potency as an antagonist of CB1/CB2 receptor agonists in CB1- and CB2-expressing cells or tissues, the manner with which it interacts with CB2 receptors providing a possible explanation for its ability to inhibit evoked immune cell migration. Delta9-THCV behaves as a potent CB2 receptor partial agonist in vitro. In contrast, it antagonizes cannabinoid receptor agonists in CB1-expressing tissues. This it does with relatively high potency and in a manner that is both tissue and ligand dependent. Delta9-THCV also interacts with CB1 receptors when administered in vivo, behaving either as a CB1 antagonist or, at higher doses, as a CB1 receptor agonist. Brief mention is also made in this review, first of the production by delta9-THC of pharmacodynamic tolerance, second of current knowledge about the extent to which delta9-THC, CBD and delta9-THCV interact with pharmacological targets other than CB1 or CB2 receptors, and third of actual and potential therapeutic applications for each of these cannabinoids.

...read moreread less

1,492 citations

Cites background from "Pharmacological actions of cannabin..."

...…release of chemical messengers, in this case the release of cytokines from immune cells and may, in addition, affect immune function by modulating immune cell migration both within and outside the central nervous system (reviewed in Walter and Stella, 2004; Cabral and Staab, 2005; Pertwee, 2005a)....
[...]
...British Journal of Pharmacology (2008) 153 199–215 other CB1/CB2 receptor agonists (reviewed in Pertwee, 2004c, 2005a)....
[...]
...…some disorders that appear to trigger an upregulation of cannabinoid receptors selectively in cells or tissues in which these receptors mediate symptom relief and/or inhibition of disease progression when activated by endogenously released or exogenously administered cannabinoids (Pertwee, 2005b)....
[...]
...…of exogenously administered anandamide (Wiley et al., 2005b), it may be that it has the capacity to render patients with certain disorders tolerant to this endocannabinoid when it is being released in a manner that is either protective or causing unwanted effects (reviewed in Pertwee, 2005b)....
[...]
...…directed at identifying the mechanisms that under- lie some of the other potentially beneficial effects of CBD, for example its anticonvulsant, antipsychotic, anxiolytic, anti- emetic, neuroprotective, anticancer and sleep-promoting effects (Pertwee, 2004b, 2005c; Parker et al., 2005)....
[...]

Journal Article•DOI•

International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid Receptors and Their Ligands: Beyond CB1 and CB2

[...]

Roger G. Pertwee¹, Allyn C. Howlett, Mary E. Abood, Stephen P.H. Alexander, V. Di Marzo, Maurice R. Elphick, Peter J. Greasley, Harald S. Hansen, George Kunos, Ken Mackie, Raphael Mechoulam, Ruth Alexandra Ross - Show less +8 more•Institutions (1)

University of Aberdeen¹

01 Dec 2010-Pharmacological Reviews

TL;DR: This review summarizes current data indicating the extent to which cannabinoid receptor ligands undergo orthosteric or allosteric interactions with non- CB1, non-CB2 established GPCRs, deorphanized receptors such as GPR55, ligand-gated ion channels, transient receptor potential (TRP) channels, and other ion channels or peroxisome proliferator-activated nuclear receptors.

...read moreread less

Abstract: There are at least two types of cannabinoid receptors (CB1 and CB2). Ligands activating these G protein-coupled receptors (GPCRs) include the phytocannabinoid Δ9-tetrahydrocannabinol, numerous synthetic compounds, and endogenous compounds known as endocannabinoids. Cannabinoid receptor antagonists have also been developed. Some of these ligands activate or block one type of cannabinoid receptor more potently than the other type. This review summarizes current data indicating the extent to which cannabinoid receptor ligands undergo orthosteric or allosteric interactions with non-CB1, non-CB2 established GPCRs, deorphanized receptors such as GPR55, ligand-gated ion channels, transient receptor potential (TRP) channels, and other ion channels or peroxisome proliferator-activated nuclear receptors. From these data, it is clear that some ligands that interact similarly with CB1 and/or CB2 receptors are likely to display significantly different pharmacological profiles. The review also lists some criteria that any novel “CB3” cannabinoid receptor or channel should fulfil and concludes that these criteria are not currently met by any non-CB1, non-CB2 pharmacological receptor or channel. However, it does identify certain pharmacological targets that should be investigated further as potential CB3 receptors or channels. These include TRP vanilloid 1, which possibly functions as an ionotropic cannabinoid receptor under physiological and/or pathological conditions, and some deorphanized GPCRs. Also discussed are 1) the ability of CB1 receptors to form heteromeric complexes with certain other GPCRs, 2) phylogenetic relationships that exist between CB1/CB2 receptors and other GPCRs, 3) evidence for the existence of several as-yet-uncharacterized non-CB1, non-CB2 cannabinoid receptors; and 4) current cannabinoid receptor nomenclature.

...read moreread less

1,439 citations

Cites background or methods from "Pharmacological actions of cannabin..."

...Rimonabant, which is a low-affinity antagonist of the vascular putative abn-CBD receptor (for review, see Pertwee 2005a; Ross, 2009), had no effect on GPR18-mediated microglial migration at concentrations up to 1 M (McHugh et al., 2010)....
[...]
...As to CB2 receptors, these are located predominantly in immune cells and, when activated, can modulate immune cell migration and cytokine release both outside and within the brain (for review, see Howlett et al., 2002; Cabral and Staab, 2005; Pertwee, 2005a)....
[...]
...H.2, lack significant affinity for the CB1 receptor (for review, see Pertwee, 2004, 2005a)....
[...]
...Several other compounds have been reported to behave as neutral cannabinoid CB1 receptor antagonists (Pertwee, 2005a)....
[...]
...Although these compounds lack any ability to activate CB1 receptors when administered alone, there is evidence that in some CB1 receptor-containing tissues, they can induce responses opposite in direction from those elicited by a CB1 receptor agonist (Pertwee, 2005c; Fong et al., 2007)....
[...]

Control of pain initiation by endogenous cannabinoids

[...]

Antonio Calignano¹, G. L A Ranna, Andrea Giuffrida¹, Daniele Piomelli¹•Institutions (1)

University of Naples Federico II¹

01 Jan 1999

TL;DR: In this article, anandamide attenuates the pain behavior produced by chemical damage to cutaneous tissue by interacting with CB1-like cannabinoid receptors located outside the central nervous system.

...read moreread less

Abstract: The potent analgesic effects of cannabis-like drugs and the presence of CB1-type cannabinoid receptors in pain-processing areas of the brain and spinal cord, indicate that endogenous cannabinoids such as anandamide may contribute to the control of pain transmission within the central nervous system (CNS). Here we show that anandamide attenuates the pain behaviour produced by chemical damage to cutaneous tissue by interacting with CB1-like cannabinoid receptors located outside the CNS. Palmitylethanolamide (PEA), which is released together with anandamide from a common phospholipid precursor, exerts a similar effect by activating peripheral CB2-like receptors. When administered together, the two compounds act synergistically, reducing pain responses 100-fold more potently than does each compound alone. Gas-chromatography/mass-spectrometry measurements indicate that the levels of anandamide and PEA in the skin are enough to cause a tonic activation of local cannabinoid receptors. In agreement with this possibility, the CB1 antagonist SR141716A and the CB2 antagonist SR144528 prolong and enhance the pain behaviour produced by tissue damage. These results indicate that peripheral CB1-like and CB2-like receptors participate in the intrinsic control of pain initiation and that locally generated anandamide and PEA may mediate this effect.

...read moreread less

918 citations

Journal Article•DOI•

Cannabinoid pharmacology: the first 66 years

[...]

Roger G. Pertwee¹•Institutions (1)

University of Aberdeen¹

01 Jan 2006-British Journal of Pharmacology

TL;DR: Research into the pharmacology of individual cannabinoids that began in the 1940s is concisely reviewed and it is described how this pharmacological research led to the discovery of cannabinoid CB1 and CB2 receptors and of endogenous ligands for these receptors.

...read moreread less

Abstract: Research into the pharmacology of individual cannabinoids that began in the 1940s, several decades after the presence of a cannabinoid was first detected in cannabis, is concisely reviewed. Also described is how this pharmacological research led to the discovery of cannabinoid CB1 and CB2 receptors and of endogenous ligands for these receptors, to the development of CB1- and CB2-selective agonists and antagonists and to the realization that the endogenous cannabinoid systemhas significant roles in both health and disease, and that drugs which mimic, augment or block the actions of endogenously released cannabinoids must have important therapeutic applications. Some goals for future research are identified. British Journal of Pharmacology (2006) 147, S163–S171. doi:10.1038/sj.bjp.0706406

...read moreread less

604 citations

Cites background from "Pharmacological actions of cannabin..."

...Although often regarded as peripheral receptors, CB2 receptors have been detected in the central nervous system, for example, on microglial cells (reviewed in Howlett et al., 2002; Pertwee, 2005b)....
[...]
...Since the discovery of CB1 and CB2 receptors, a great deal has become known about how these receptors signal and about their roles (reviewed in Howlett et al., 2002; Howlett, 2005; Pertwee, 2005b)....
[...]
...…disorders in which there is a ‘protective’ upregulation of cannabinoid receptor expression level and/or coupling efficiency, by administering a partial cannabinoid British Journal of Pharmacology vol 147 (S1) receptor agonist such as D9-THC rather than a full agonist (reviewed in Pertwee, 2005c)....
[...]
...In addition, there is now considerable interest in developing new strategies that might improve the benefit to risk ratio of cannabinoid receptor agonists (reviewed in Pertwee, 2005c)....
[...]
...Allosteric CB1 receptor antagonists have potential as medicines too, as do CB2 receptor inverse agonists since evidence has recently emerged that these can ameliorate inflammation by inhibiting immune cell migration (reviewed in Pertwee, 2005c)....
[...]

1
2
3
4
…
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119

Collapse

References

PDF

Open Access

More filters

Journal Article•DOI•

International Union of Pharmacology: Approaches to the Nomenclature of Voltage-Gated Ion Channels

[...]

William A. Catterall¹, K. G. Chandy², David E. Clapham³, George A. Gutman², Franz Hofmann⁴, Anthony J. Harmar⁵, Darrell R. Abernethy⁶, Michael Spedding - Show less +4 more•Institutions (6)

University of Washington¹, University of California, Irvine², Howard Hughes Medical Institute³, Ludwig Maximilian University of Munich⁴, University of Edinburgh⁵, National Institutes of Health⁶

01 Dec 2003-Pharmacological Reviews

TL;DR: This issue of Pharmacological Reviews includes a new venture in the collaboration between the International Union of Pharmacology (IUPHAR) and the American Society for Pharmacology and Experimental Therapeutics (ASPET), in that a new classification of voltage-gated ion channels is outlined.

...read moreread less

Abstract: This issue of Pharmacological Reviews includes a new venture in the collaboration between the International Union of Pharmacology (IUPHAR) and the American Society for Pharmacology and Experimental Therapeutics (ASPET), in that a new classification of voltage-gated ion channels is outlined in this

...read moreread less

7,389 citations

Journal Article•DOI•

Isolation and structure of a brain constituent that binds to the cannabinoid receptor

[...]

William A. Devane¹, Lumir Hanus¹, Aviva Breuer¹, Roger G. Pertwee², Lesley A. Stevenson², Graeme Griffin², Dan Gibson¹, Asher Mandelbaum³, A. Etinger³, Raphael Mechoulam¹ - Show less +6 more•Institutions (3)

Hebrew University of Jerusalem¹, University of Aberdeen², Technion – Israel Institute of Technology³

18 Dec 1992-Science

TL;DR: In this article, an arachidonylethanthanolamide (anandamide) was identified in a screen for endogenous ligands for the cannabinoid receptor and its structure was determined by mass spectrometry and nuclear magnetic resonance spectroscopy and confirmed by synthesis.

...read moreread less

Abstract: Arachidonylethanolamide, 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 radiolabeled cannabinoid probe to synaptosomal membranes in a manner typical of competitive ligands and produced a concentration-dependent inhibition of the electrically evoked twitch response to the mouse vas deferens, a characteristic effect of psychotropic cannabinoids. These properties suggest that anandamide may function as a natural ligand for the cannabinoid receptor.

...read moreread less

5,283 citations

"Pharmacological actions of cannabin..." refers background in this paper

...Also, palmitoylethanolamide does not bind to or activate CB1 receptors at concentrations below 1 or 10 μM (Devane et al. 1992; Felder et al. 1993; Griffin et al. 2000; Lambert et al. 1999; Showalter et al. 1996)....
[...]
...Also, palmitoylethanolamide does not bind to or activate CB1 receptors at concentrations below 1 or 10 µM (Devane et al. 1992; Felder et al. 1993; Griffin et al. 2000; Lambert et al. 1999; Showalter et al. 1996)....
[...]

Journal Article•DOI•

Structure of a cannabinoid receptor and functional expression of the cloned cDNA

[...]

Lisa A. Matsuda¹, Stephen J. Lolait¹, Michael J. Brownstein¹, Alice C. Young¹, Tom I. Bonner¹ - Show less +1 more•Institutions (1)

National Institutes of Health¹

09 Aug 1990-Nature

TL;DR: The cloning and expression of a complementary DNA that encodes a G protein-coupled receptor that is involved in cannabinoid-induced CNS effects (including alterations in mood and cognition) experienced by users of marijuana are suggested.

...read moreread less

Abstract: Marijuana and many of its constituent cannabinoids influence the central nervous system (CNS) in a complex and dose-dependent manner. Although CNS depression and analgesia are well documented effects of the cannabinoids, the mechanisms responsible for these and other cannabinoid-induced effects are not so far known. The hydrophobic nature of these substances has suggested that cannabinoids resemble anaesthetic agents in their action, that is, they nonspecifically disrupt cellular membranes. Recent evidence, however, has supported a mechanism involving a G protein-coupled receptor found in brain and neural cell lines, and which inhibits adenylate cyclase activity in a dose-dependent, stereoselective and pertussis toxin-sensitive manner. Also, the receptor is more responsive to psychoactive cannabinoids than to non-psychoactive cannabinoids. Here we report the cloning and expression of a complementary DNA that encodes a G protein-coupled receptor with all of these properties. Its messenger RNA is found in cell lines and regions of the brain that have cannabinoid receptors. These findings suggest that this protein is involved in cannabinoid-induced CNS effects (including alterations in mood and cognition) experienced by users of marijuana.

...read moreread less

4,806 citations

"Pharmacological actions of cannabin..." refers background in this paper

...Cannabinol also behaves as a partial agonist at CB1 receptors but has even less relative intrinsic activity than (–)-∆9-THC (Howlett 1987; Matsuda et al. 1990; Petitet et al. 1997, 1998)....
[...]
...Of these, (–)-∆8-THC resembles (–)-∆9-THC both in its CB1 and CB2 receptor affinities (Table 2) and in its relative intrinsic activity at the CB1 receptor (Gérard et al. 1991; Howlett and Fleming 1984; Matsuda et al. 1990)....
[...]

Journal Article•DOI•

Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors.

[...]

Raphael Mechoulam¹, Shimon Ben-Shabat¹, Lumir Hanus¹, Moshe Ligumsky¹, Norbert E. Kaminski², Anthony R. Schatz³, Asher Gopher⁴, Shlomo Almog⁴, Billy R. Martin³, David R. Compton³, Roger G. Pertwee⁵, Graeme Griffin⁵, Michael Bayewitch⁶, Jacob Barg⁶, Zvi Vogel⁶ - Show less +11 more•Institutions (6)

Hebrew University of Jerusalem¹, Michigan State University², VCU Medical Center³, Sheba Medical Center⁴, University of Aberdeen⁵, Weizmann Institute of Science⁶

29 Jun 1995-Biochemical Pharmacology

TL;DR: Upon intravenous administration to mice, 2-Ara-Gl caused the typical tetrad of effects produced by THC: antinociception, immobility, reduction of spontaneous activity, and lowering of the rectal temperature.

...read moreread less

2,764 citations

Journal Article•DOI•

International Union of Pharmacology. XXVII. Classification of Cannabinoid Receptors

[...]

Allyn C. Howlett¹, Francis Barth, Tom I. Bonner, Guy A. Cabral, Pierre Casellas, William A. Devane, Christian C. Felder, Miles Herkenham, Ken Mackie, Billy R. Martin, Raphael Mechoulam, Roger G. Pertwee - Show less +8 more•Institutions (1)

North Carolina Central University¹

01 Jun 2002-Pharmacological Reviews

TL;DR: It is considered premature to rename cannabinoid receptors after an endogenous agonist as is recommended by the International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification, because pharmacological evidence for the existence of additional types of cannabinoid receptor is emerging and other kinds of supporting evidence are still lacking.

...read moreread less

Abstract: Two types of cannabinoid receptor have been discovered so far, CB(1) (2.1: CBD:1:CB1:), cloned in 1990, and CB(2) (2.1:CBD:2:CB2:), cloned in 1993. Distinction between these receptors is based on differences in their predicted amino acid sequence, signaling mechanisms, tissue distribution, and sensitivity to certain potent agonists and antagonists that show marked selectivity for one or the other receptor type. Cannabinoid receptors CB(1) and CB(2) exhibit 48% amino acid sequence identity. Both receptor types are coupled through G proteins to adenylyl cyclase and mitogen-activated protein kinase. CB(1) receptors are also coupled through G proteins to several types of calcium and potassium channels. These receptors exist primarily on central and peripheral neurons, one of their functions being to inhibit neurotransmitter release. Indeed, endogenous CB(1) agonists probably serve as retrograde synaptic messengers. CB(2) receptors are present mainly on immune cells. Such cells also express CB(1) receptors, albeit to a lesser extent, with both receptor types exerting a broad spectrum of immune effects that includes modulation of cytokine release. Of several endogenous agonists for cannabinoid receptors identified thus far, the most notable are arachidonoylethanolamide, 2-arachidonoylglycerol, and 2-arachidonylglyceryl ether. It is unclear whether these eicosanoid molecules are the only, or primary, endogenous agonists. Hence, we consider it premature to rename cannabinoid receptors after an endogenous agonist as is recommended by the International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. Although pharmacological evidence for the existence of additional types of cannabinoid receptor is emerging, other kinds of supporting evidence are still lacking.

...read moreread less

2,619 citations

"Pharmacological actions of cannabin..." refers background or methods in this paper

...In vivo bioassays that provide measures of other CB1 receptor-mediated effects in animals, for example changes in memory, have also been developed (reviewed in Howlett et al. 2002; see also the chapter by Riedel and Davies, this volume)....
[...]
...…contractile transmitter release (Schlicker et al. 2003; Trendelenburg et al. 2000) and of the contractions caused by this release (reviewed in Howlett et al. 2002; Pertwee 1997; Pertwee et al. 1996a; Schlicker and Kathmann 2001) are called isolated nerve–smooth muscle preparations....
[...]
...Results from pharmacological experiments with rats and mice performed by Sandra Welch’s group also suggest that there may be more than one subtype of CB1 receptor (reviewed in Howlett et al. 2002; Pertwee 2001)....
[...]
...…isolated mesenteric arterial beds or isolated mesenteric arterial segments, for the presence in these tissues of non-CB1, non-CB2 receptors with which anandamide and methanandamide can interact to induce a relaxant effect (reviewed in Howlett et al. 2002; Pertwee 2004a; Wiley and Martin 2002)....
[...]
...As discussed in greater detail elsewhere (Hájos and Freund 2002b; Howlett et al. 2002; Pertwee 1999b, 2004a; Pertwee and Ross 2002; Wiley and Martin 2002), evidence is emerging that in addition to CB1 and CB2 receptors, there are other pharmacological targets in mammalian tissues with which at…...
[...]