Tag Archives: phytocannabinoid

Acute Δ9-tetrahydrocannabinol blocks gastric hemorrhages induced by the nonsteroidal anti-inflammatory drug diclofenac sodium in mice.

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“Nonsteroidal anti-inflammatory drugs (NSAIDs), which are among the most widely used analgesics in the world, cause gastrointestinal inflammation that is potentially life-threatening.

Although inhibitors of endocannabinoid catabolic enzymes protect against gastropathy in fasted NSAID-treated mice, the gastroprotective effects of Δ9-tetrahydrocannabinol (THC), the primary psychoactive component of marijuana, have yet to be investigated…

 These data indicate that the phytocannabinoid Δ9-THC protects against diclofenac-induced gastric inflammatory tissue damage at doses insufficient to cause common cannabinoid side effects.”

http://www.ncbi.nlm.nih.gov/pubmed/23769745

Facilitation of contextual fear memory extinction and anti-anxiogenic effects of AM404 and cannabidiol in conditioned rats.

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“The present study investigated the central effects of the eCB uptake/metabolism inhibitor AM404 and the phytocannabinoid cannabidiol (CBD) on the extinction of contextual fear memories in rats…

… In conclusion, CBD, a non-psychoactive phytocannabinoid could be an interesting pharmacological approach to reduce the anxiogenic effects of stress and promote the extinction of fear memories.”

http://www.ncbi.nlm.nih.gov/pubmed/18706790

Cannabidiol Reduces Aβ-Induced Neuroinflammation and Promotes Hippocampal Neurogenesis through PPARγ Involvement

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“CBD blunted neuroinflammation sustained by astrocytes through PPARγ selective activation in vitro and in vivo.

Results from the present study prove the selective involvement of PPARγ in the anti-inflammatory and neuroprotective effects of CBD here observed either in vitro and in vivo. In addition, CBD significantly promoted neurogenesis in Aβ injured rat hippocampi, much expanding its already wide spectrum of beneficial actions exerted in AD models, a non negligible effect, due to its capability to activate PPARγ.

In conclusion, results of the present research demonstrate that CBD may exert protective functions through a PPARγ dependent activation, which leads to a reduction in reactive gliosis and consequently in neurodegeneration. Moreover, in the current experimental conditions this phytocannabinoid appears to stimulate neurogenesis since it increases DCX immunopositive cell proliferation rate in rat DG.

Innovative therapeutic approaches which could significantly improve AD course require new molecules that will be able to have an impact on different pathological pathways, which converge at the progressive neurological decline. CBD has shown a capability to profoundly reduce reactive astrogliosis and to guarantee both direct and indirect neuronal protection in Aβ induced neuroinflammation/neurodegeration. So far, the lack of understanding of the precise molecular mechanism involved in CBD pharmacological actions, has had limited interest and has puzzled investigators.

Currently, findings of the present study throw some light on the issue, and frame CBD as a new PPARγ activator.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230631/

Cannabidiol and other cannabinoids reduce microglial activation in vitro and in vivo: relevance to Alzheimer’s disease.

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“Microglial activation is an invariant feature of Alzheimer’s disease (AD). It is noteworthy that cannabinoids are neuroprotective by preventing β-amyloid (Aβ)-induced microglial activation both in vitro and in vivo… the phytocannabinoid cannabidiol (CBD) has shown anti-inflammatory properties in different paradigms…

Cannabinoids, whether plant-derived, synthetic, or endocannabinoids, exert their functions through activation of cannabinoid receptors, two of which have been well characterized to date: CB1 and CB2. Cannabinoids are neuroprotective against excitotoxicity and acute brain damage, both in vitro and in vivo. Several mechanisms account for the neuroprotection afforded by this type of drug such as blockade of excitotoxicity, reduction of calcium influx, antioxidant properties of the compounds, or enhanced trophic factor support. A decrease in proinflammatory mediators brought about by cannabinoids may be also involved in their neuroprotection… Cannabidiol (CBD), the major plant-derived nonpsychotropic constituent of marijuana, is of potential therapeutic interest in different disease conditions (e.g., inflammation)…

…this kind of drug with neuroprotective and anti-inflammatory effects may be of interest in the prevention of AD inflammation, in particular CB2-selective agonists, which are devoid of psychoactive effects…

Cannabidiol and other cannabinoids reduce microglial activation in vitro and in vivo…

CBD is able to modulate microglial cell function in vitro and induce beneficial effects in an in vivo model of AD.

Given that CBD lacks psychoactivity, it may represent a novel therapeutic approach for this neurological disease.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3102548/

Contrasting protective effects of cannabinoids against oxidative stress and amyloid-β evoked neurotoxicity in vitro.

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“Cannabinoids have been widely reported to have neuroprotective properties in vitro and in vivo. In this study we compared the effects of CB1 and CB2 receptor-selective ligands, the endocannabinoid anandamide and the phytocannabinoid cannabidiol, against oxidative stress and the toxic hallmark Alzheimer’s protein, β-amyloid (Aβ)…

 …the endocannabinoid anandamide protects neuronal cells from Aβ exposure via a pathway unrelated to CB1 or CB2 receptor activation…protective effect of cannabidiol against oxidative stress…

…divergent pathways for neuroprotection of these two cannabinoids.”

http://www.ncbi.nlm.nih.gov/pubmed/22233683

The therapeutic potential of the endocannabinoid system for Alzheimer’s disease.

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“Based on the complex pathology of AD, a preventative, multimodal drug approach targeting a combination of pathological AD symptoms appears ideal. Importantly, cannabinoids show anti-inflammatory, neuroprotective and antioxidant properties and have immunosuppressive effects. Thus, the cannabinoid system should be a prime target for AD therapy. The cannabinoid receptor 2 appears to be a promising candidate but its role in AD has to be investigated cautiously. Furthermore, the phytocannabinoid cannabidiol is of particular interest as it lacks the psychoactive and cognition-impairing properties of other cannabinoids. In conclusion, future research should focus on the evaluation of the effects of manipulations to the endocannabinoid system in established animal models for AD, combined with early-phase studies in humans.”

http://www.ncbi.nlm.nih.gov/pubmed/22448595

Symptom-relieving and neuroprotective effects of the phytocannabinoid Δ9-THCV in animal models of Parkinson’s disease

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“Previous findings have indicated that a cannabinoid, such as Δ(9)-THCV, which has antioxidant properties and the ability to activate CB(2) receptors but to block CB(1) , might be a promising therapy for alleviating symptoms and delaying neurodegeneration in Parkinson’s disease (PD).

…Given its antioxidant properties and its ability to activate CB(2) but to block CB(1) receptors, Δ(9)-THCV has a promising pharmacological profile for delaying disease progression in PD and also for ameliorating parkinsonian symptoms…

Conclusion

In summary, given its antioxidant properties and its ability to activate CB2 but block CB1 receptors at a dose of 2 mg·kg−1, Δ9-THCV seems to have an interesting and therapeutically promising pharmacological profile. Thus, in contrast to other phytocannabinoids that have been investigated to date, it shows promise both for the treatment of disease progression in PD and for the relief of PD symptoms. This represents an important advance in the search for potential novel anti-parkinsonian agents, since Δ9-THCV administered alone or in combination with CBD may provide a much needed improved treatment for PD.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165958/

Antihyperalgesic effect of a Cannabis sativa extract in a rat model of neuropathic pain: mechanisms involved.

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Abstract

“This study aimed to give a rationale for the employment of phytocannabinoid formulations to treat neuropathic pain. It was found that a controlled cannabis extract, containing multiple cannabinoids, in a defined ratio, and other non-cannabinoid fractions (terpenes and flavonoids) provided better antinociceptive efficacy than the single cannabinoid given alone, when tested in a rat model of neuropathic pain. The results also demonstrated that such an antihyperalgesic effect did not involve the cannabinoid CB1 and CB2 receptors, whereas it was mediated by vanilloid receptors TRPV1. The non-psychoactive compound, cannabidiol, is the only component present at a high level in the extract able to bind to this receptor: thus cannabidiol was the drug responsible for the antinociceptive behaviour observed. In addition, the results showed that after chronic oral treatment with cannabis extract the hepatic total content of cytochrome P450 was strongly inhibited as well as the intestinal P-glycoprotein activity. It is suggested that the inhibition of hepatic metabolism determined an increased bioavailability of cannabidiol resulting in a greater effect. However, in the light of the well known antioxidant and antiinflammatory properties of terpenes and flavonoids which could significantly contribute to the therapeutic effects, it cannot be excluded that the synergism observed might be achieved also in the absence of the cytochrome P450 inhibition.”

http://www.ncbi.nlm.nih.gov/pubmed/18618522

Δ⁹-Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats.

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“PURPOSE:

We assessed the anticonvulsant potential of the phytocannabinoid Δ⁹-tetrahydrocannabivarin (Δ⁹-THCV) by investigating its effects in an in vitro piriform cortex (PC) brain slice model of epileptiform activity, on cannabinoid CB1 receptor radioligand-binding assays and in a generalized seizure model in rats.”

“DISCUSSION:

These data demonstrate that Δ⁹-THCV exerts antiepileptiform and anticonvulsant properties, actions that are consistent with a CB1 receptor-mediated mechanism and suggest possible therapeutic application in the treatment of pathophysiologic hyperexcitability states.”

http://www.ncbi.nlm.nih.gov/pubmed/20196794

Inhibitory effect of cannabichromene, a major non-psychotropic cannabinoid extracted from Cannabis sativa, on inflammation-induced hypermotility in mice.

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“BACKGROUND AND PURPOSE:

Cannabichromene (CBC) is a major non-psychotropic phytocannabinoid that inhibits endocannabinoid inactivation and activates the transient receptor potential ankyrin-1 (TRPA1). Both endocannabinoids and TRPA1 may modulate gastrointestinal motility. Here, we investigated the effect of CBC on mouse intestinal motility in physiological and pathological states.”

“CONCLUSION AND IMPLICATIONS:

CBC selectively reduces inflammation-induced hypermotility in vivo in a manner that is not dependent on cannabinoid receptors or TRPA1.”

http://www.ncbi.nlm.nih.gov/pubmed/22300105