Δ9-Tetrahydrocannabinol and cannabidiol modulate mitogen-induced tryptophan degradation and neopterin formation in peripheral blood mononuclear cells in vitro

Jenny, M; Santer, Elisabeth; Pirich, Eberhard; Schennach, Harald; Fuchs, Dietmar

doi:10.1016/j.jneuroim.2008.12.004

Cited by 52 publications

(40 citation statements)

References 50 publications

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“…Previously, we have demonstrated that both cannabinoids, THC and CBD, modulate mitogen-induced Th1-type immune responses in PBMC in a biphasic manner [19]. In this study, we could show that mitogen induced production of neopterin, a marker of cellular immunity, was dose-dependently suppressed upon treatment of PBMC with THC or CBD.…”

Section: Introductionsupporting

confidence: 50%

“…Results of our in vitro study demonstrated that THC and CBD interfere with immunological pathways stimulated by pro-inflammatory Th1-type cytokine IFN-γ, which further emphasizes their well known anti-inflammatory capacity [19]. The suppressive effect of THC and CBD on cytokine-induced tryptophan degradation may constitute an additional mechanism by which antidepressive effects of cannabinoids might be linked to the serotonergic system.…”

Section: Discussionmentioning

confidence: 84%

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The Potential Role of Cannabinoids in Modulating Serotonergic Signaling by Their Influence on Tryptophan Metabolism

et al. 2010

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Phytocannabinoids present in Cannabis plants are well known to exert potent anti-inflammatory and immunomodulatory effects. Previously, we have demonstrated that the psychoactive Δ9-tetrahydrocannabinol (THC) and the non-psychotropic cannabidiol (CBD) modulate mitogen-induced Th1-type immune responses in peripheral blood mononuclear cells (PBMC). The suppressive effect of both cannabinoids on mitogen-induced tryptophan degradation mediated by indoleamine-2,3-dioxygenase (IDO), suggests an additional mechanism by which antidepressive effects of cannabinoids might be linked to the serotonergic system. Here, we will review the role of tryptophan metabolism in the course of cell mediated immune responses and the relevance of cannabinoids in serotonergic signaling. We conclude that in particular the non-psychotropic CBD might be useful for the treatment of mood disorders in patients with inflammatory diseases, since this cannabinoid seems to be safe and its effects on activation-induced tryptophan degradation by CBD were more potent as compared to THC.

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Section: Introductionsupporting

confidence: 50%

Section: Discussionmentioning

confidence: 84%

The Potential Role of Cannabinoids in Modulating Serotonergic Signaling by Their Influence on Tryptophan Metabolism

et al. 2010

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“…CBD can exert biphasic effects on the kynurenine/ tryptophan pathways, causing activation at < 1 μM but inhibition at higher concentrations [72]. A key enzyme in this pathway is IDO, which, when activated by inflammatory mediators, might not only increase tryptophan degradation, and thus 5-HT depletion, but also the production of metabolites that could induce oxidative stress [94,214].…”

Section: Cbd Enzyme Targets In Neurodegenerationmentioning

confidence: 99%

Molecular Targets of Cannabidiol in Neurological Disorders

Bih

Chen

Nunn³

et al. 2015

Neurotherapeutics

449

323

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Cannabis has a long history of anecdotal medicinal use and limited licensed medicinal use. Until recently, alleged clinical effects from anecdotal reports and the use of licensed cannabinoid medicines are most likely mediated by tetrahydrocannabinol by virtue of: 1) this cannabinoid being present in the most significant quantities in these preparations; and b) the proportion:potency relationship between tetrahydrocannabinol and other plant cannabinoids derived from cannabis. However, there has recently been considerable interest in the therapeutic potential for the plant cannabinoid, cannabidiol (CBD), in neurological disorders but the current evidence suggests that CBD does not directly interact with the endocannabinoid system except in vitro at supraphysiological concentrations. Thus, as further evidence for CBD's beneficial effects in neurological disease emerges, there remains an urgent need to establish the molecular targets through which it exerts its therapeutic effects. Here, we conducted a systematic search of the extant literature for original articles describing the molecular pharmacology of CBD. We critically appraised the results for the validity of the molecular targets proposed. Thereafter, we considered whether the molecular targets of CBD identified hold therapeutic potential in relevant neurological diseases. The molecular targets identified include numerous classical ion channels, receptors, transporters, and enzymes. Some CBD effects at these targets in in vitro assays only manifest at high concentrations, which may be difficult to achieve in vivo, particularly given CBD's relatively poor bioavailability. Moreover, several targets were asserted through experimental designs that demonstrate only correlation with a given target rather than a causal proof. When the molecular targets of CBD that were physiologically plausible were considered for their potential for exploitation in neurological therapeutics, the results were variable. In some cases, the targets identified had little or no established link to the diseases considered. In others, molecular targets of CBD were entirely consistent with those already actively exploited in relevant, clinically used, neurological treatments. Finally, CBD was found to act upon a number of targets that are linked to neurological therapeutics but that its actions were not consistent withmodulation of such targets that would derive a therapeutically beneficial outcome. Overall, we find that while >65 discrete molecular targets have been reported in the literature for CBD, a relatively limited number represent plausible targets for the drug's action in neurological disorders when judged by the criteria we set. We conclude that CBD is very unlikely to exert effects in neurological diseases through modulation of the endocannabinoid system. Moreover, a number of other molecular targets of CBD reported in the literature are unlikely to be of relevance owing to effects only being observed at supraphysiological concentrations. Of interest and after excludin...

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“…5HT 1A ) [18, 19, 28], adenosine uptake [37], nuclear receptors of the PPAR family (i.e. PPAR‐γ) [38, 39] and many other pharmacological targets (see Table 1 including references [40–56]). In part, this information derives from numerous studies directed at identifying the pharmacological actions that CBD produces in vitro .…”

Section: Overview On the Mechanisms Of Action Of Cbdmentioning

confidence: 99%

Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid?

Fernández‐Ruiz

Sagredo

Pazos

et al. 2013

Brit J Clinical Pharma

283

196

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Cannabidiol (CBD) is a phytocannabinoid with therapeutic properties for numerous disorders exerted through molecular mechanisms that are yet to be completely identified. CBD acts in some experimental models as an anti‐inflammatory, anticonvulsant, anti‐oxidant, anti‐emetic, anxiolytic and antipsychotic agent, and is therefore a potential medicine for the treatment of neuroinflammation, epilepsy, oxidative injury, vomiting and nausea, anxiety and schizophrenia, respectively. The neuroprotective potential of CBD, based on the combination of its anti‐inflammatory and anti‐oxidant properties, is of particular interest and is presently under intense preclinical research in numerous neurodegenerative disorders. In fact, CBD combined with Δ9‐tetrahydrocannabinol is already under clinical evaluation in patients with Huntington's disease to determine its potential as a disease‐modifying therapy. The neuroprotective properties of CBD do not appear to be exerted by the activation of key targets within the endocannabinoid system for plant‐derived cannabinoids like Δ9‐tetrahydrocannabinol, i.e. CB1 and CB2 receptors, as CBD has negligible activity at these cannabinoid receptors, although certain activity at the CB2 receptor has been documented in specific pathological conditions (i.e. damage of immature brain). Within the endocannabinoid system, CBD has been shown to have an inhibitory effect on the inactivation of endocannabinoids (i.e. inhibition of FAAH enzyme), thereby enhancing the action of these endogenous molecules on cannabinoid receptors, which is also noted in certain pathological conditions. CBD acts not only through the endocannabinoid system, but also causes direct or indirect activation of metabotropic receptors for serotonin or adenosine, and can target nuclear receptors of the PPAR family and also ion channels.

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Δ9-Tetrahydrocannabinol and cannabidiol modulate mitogen-induced tryptophan degradation and neopterin formation in peripheral blood mononuclear cells in vitro

Cited by 52 publications

References 50 publications

The Potential Role of Cannabinoids in Modulating Serotonergic Signaling by Their Influence on Tryptophan Metabolism

The Potential Role of Cannabinoids in Modulating Serotonergic Signaling by Their Influence on Tryptophan Metabolism

Molecular Targets of Cannabidiol in Neurological Disorders

Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid?

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