A comparison of the pharmacological activity in man of intravenously administered 1368-11368-11368-1, cannabinol, and cannabidiol

Perez‐Reyes, Mario; Timmons, Michael B.; Davis, Kenneth; Wall, E. M.

doi:10.1007/bf01922823

Cited by 163 publications

(68 citation statements)

References 2 publications

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“…Such a model is reminiscent of many feed-forward mechanisms that lead to local recruitment of immune cells and amplification of inflammation. We also show that CBN and CBD, two nonpsychotropic bioactive compounds of marijuana (Perez-Reyes et al, 1973), may antagonize the 2-AG-induced recruitment of microglial cells. This is in agreement with the fact that nabilone, a synthetic analog of THC, produces minimal palliative effects against multiple sclerosis symptoms, whereas smoking cannabis is reported to be beneficial (Martyn et al, 1995;Consroe et al, 1997).…”

Section: Discussionmentioning

confidence: 53%

“…Because CBN and CBD do not have significant intrinsic activity on CB1 receptors (Felder et al, 1995;Showalter et al, 1996), these compounds do not produce psychotropic and adverse side effects (Perez-Reyes et al, 1973), which makes them promising candidates as anti-inflammatory therapeutics. It should be emphasized that plant cannabinoids often act as partial agonists on cannabinoid receptors (Howlett et al, 2002), which suggests that they might antagonize the efficacious effects of certain endocannabinoids (i.e., the endogenous cannabinoid ligands produced by cells) (Piomelli et al, 1998;Stella and Piomelli, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Nonpsychotropic Cannabinoid Receptors Regulate Microglial Cell Migration

Walter¹,

Franklin²,

Witting³

et al. 2003

J. Neurosci.

598

543

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During neuroinflammation, activated microglial cells migrate toward dying neurons, where they exacerbate local cell damage. The signaling molecules that trigger microglial cell migration are poorly understood. In this paper, we show that pathological overstimulation of neurons by glutamate plus carbachol dramatically increases the production of the endocannabinoid 2-arachidonylglycerol (2-AG) but only slightly increases the production of anandamide and does not affect the production of two putative endocannabinoids, homo-␥-linolenylethanolamide and docosatetraenylethanolamide. We further show that pathological stimulation of microglial cells with ATP also increases the production of 2-AG without affecting the amount of other endocannabinoids. Using a Boyden chamber assay, we provide evidence that 2-AG triggers microglial cell migration. This effect of 2-AG occurs through CB2 and abnormal-cannabidiolsensitive receptors, with subsequent activation of the extracellular signal-regulated kinase 1/2 signal transduction pathway. It is important to note that cannabinol and cannabidiol, two nonpsychotropic ingredients present in the marijuana plant, prevent the 2-AG-induced cell migration by antagonizing the CB2 and abnormal-cannabidiol-sensitive receptors, respectively. Finally, we show that microglial cells express CB2 receptors at the leading edge of lamellipodia, which is consistent with the involvement of microglial cells in cell migration. Our study identifies a cannabinoid signaling system regulating microglial cell migration. Because this signaling system is likely to be involved in recruiting microglial cells toward dying neurons, we propose that cannabinol and cannabidiol are promising nonpsychotropic therapeutics to prevent the recruitment of these cells at neuroinflammatory lesion sites.

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Section: Discussionmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Nonpsychotropic Cannabinoid Receptors Regulate Microglial Cell Migration

Walter¹,

Franklin²,

Witting³

et al. 2003

J. Neurosci.

598

543

View full text Add to dashboard Cite

show abstract

“…13 During this period, several reports attested that CBD was unable to mimic the effects of cannabis both in animals 14 and in humans, 15,16 leading to the thought that it was an inactive cannabinoid. This thought began to change with the observation that the activity in animals of several samples of cannabis differed widely, a fact which could not be attributed only to the different delta9-THC contents of the samples.…”

Section: Inactive Cannabinoid That Interact With Delta9-thc (1970's)mentioning

confidence: 99%

Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action

Zuardi

2008

Rev. Bras. Psiquiatr.

351

302

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“…-tetrahydrocannabinol (D 9 -THC) (Perez-Reyes et al, 1973;Zuardi et al, 1982). In particular, in animal studies CBD has effects similar to anxiolytic drugs in conditioned emotional paradigms (Zuardi and Karniol, 1983), the Vogel conflict test (Musty et al, 1984), and the elevated plus maze test (Guimaraes et al, 1990;Onaivi et al, 1990).…”

mentioning

confidence: 99%

Effects of Cannabidiol (CBD) on Regional Cerebral Blood Flow

Crippa

Zuardi

Garrido

et al. 2003

Neuropsychopharmacol

257

224

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Animal and human studies have suggested that cannabidiol (CBD) may possess anxiolytic properties, but how these effects are mediated centrally is unknown. The aim of the present study was to investigate this using functional neuroimaging. Regional cerebral blood flow (rCBF) was measured at rest using 99m Tc-ECD SPECT in 10 healthy male volunteers, randomly divided into two groups of five subjects. Each subject was studied on two occasions, 1 week apart. In the first session, subjects were given an oral dose of CBD (400 mg) or placebo, in a double-blind procedure. SPECT images were acquired 90 min after drug ingestion. The Visual Analogue Mood Scale was applied to assess subjective states. In the second session, the same procedure was performed using the drug that had not been administered in the previous session. Within-subject between-condition rCBF comparisons were performed using statistical parametric mapping (SPM). CBD significantly decreased subjective anxiety and increased mental sedation, while placebo did not induce significant changes. Assessment of brain regions where anxiolytic effects of CBD were predicted a priori revealed two voxel clusters of significantly decreased ECD uptake in the CBD relative to the placebo condition (po0.001, uncorrected for multiple comparisons). These included a medial temporal cluster encompassing the left amygdala-hippocampal complex, extending into the hypothalamus, and a second cluster in the left posterior cingulate gyrus. There was also a cluster of greater activity with CBD than placebo in the left parahippocampal gyrus (po0.001). These results suggest that CBD has anxiolytic properties, and that these effects are mediated by an action on limbic and paralimbic brain areas.

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A comparison of the pharmacological activity in man of intravenously administered 1368-11368-11368-1, cannabinol, and cannabidiol

Cited by 163 publications

References 2 publications

Nonpsychotropic Cannabinoid Receptors Regulate Microglial Cell Migration

Nonpsychotropic Cannabinoid Receptors Regulate Microglial Cell Migration

Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action

Effects of Cannabidiol (CBD) on Regional Cerebral Blood Flow

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