Tag Archives: cannabis

[The endocannabinoid system as a target for the development of new drugs for cancer therapy].

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“Studies on the main bioactive components of Cannabis sativa, the cannabinoids, and particularly delta 9-tetrahydrocannabinol (THC), led to the discovery of a new endogenous signalling system that controls several physiological and pathological conditions: the endocannabinoid system. This comprises the cannabinoid receptors, their endogenous agonists–the endocannabinoids–and proteins for endocannabinoid biosynthesis and inactivation.

Recently, evidence has accumulated indicating that stimulation of cannabinoid receptors by either THC or the endocannabinoids influence the intracellular events controlling the proliferation and apoptosis of numerous types of cancer cells, thereby leading to anti-tumour effects both in vitro and in vivo.

This evidence is reviewed here and suggests that future anti-cancer therapy might be developed from our knowledge of how the endocannabinoid system controls the growth and metastasis of malignant cells.”

http://www.ncbi.nlm.nih.gov/pubmed/12723496

Cannabinoid receptor systems: therapeutic targets for tumour intervention

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Abstract

“The past decade has witnessed a rapid expansion of our understanding of the biological roles of cannabinoids and their cognate receptors. It is now certain that Delta9-tetrahydrocannabinol, the principle psychoactive component of the Cannabis sativa plant, binds and activates membrane receptors of the 7-transmembrane domain, G-protein-coupled superfamily. Several putative endocannabinoids have since been identified, including anandamide, 2-arachidonyl glycerol and noladin ether. Synthesis of numerous cannabinomimetics has also greatly expanded the repertoire of cannabinoid receptor ligands with the pharmacodynamic properties of agonists, antagonists and inverse agonists. Collectively, these ligands have proven to be powerful tools both for the molecular characterisation of cannabinoid receptors and the delineation of their intrinsic signalling pathways. Much of our understanding of the signalling mechanisms activated by cannabinoids is derived from studies of receptors expressed by tumour cells; hence, this review provides a succinct summary of the molecular pharmacology of cannabinoid receptors and their roles in tumour cell biology. Moreover, there is now a genuine expectation that the manipulation of cannabinoid receptor systems may have therapeutic potential for a diverse range of human diseases. Thus, this review also summarises the demonstrated antitumour actions of cannabinoids and indicates possible avenues for the future development of cannabinoids as antitumour agents.”

http://www.ncbi.nlm.nih.gov/pubmed/14640910

Changes in the Endocannabinoid System May Give Insight into new and Effective Treatments for Cancer

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“The endocannabinoid system comprises specific cannabinoid receptors such as Cb1 and Cb2, the endogenous ligands (anandamide and 2-arachidonyl glycerol among others) and the proteins responsible for their synthesis and degradation. This system has become the focus of research in recent years because of its potential therapeutic value several disease states. The following review describes our current knowledge of the changes that occur in the endocannabinoid system during carcinogenesis and then focuses on the effects of anandamide on various aspects of the carcinogenic process such as growth, migration, and angiogenesis in tumors from various origins.

Marijuana and its derivatives have been used in medicine for centuries, however, it was not until the isolation of the psychoactive component of Cannabis sativa (Δ9-tetrahydrocannabinol; Δ9-THC) and the subsequent discovery of the endogenous cannabinoid signaling system that research into the therapeutic value of this system reemerged. Ongoing research is determining that regulation of the endocannabinoid system may be effective in the treatment of pain (Calignano et al., 1998; Manzanares et al., 1999), glaucoma (Voth and Schwartz, 1997), and neurodegenerative disorders such as Parkinson’s disease (Piomelli et al., 2000) and multiple sclerosis (Baker et al., 2000). In addition, cannabinoids might be effective anti-tumoral agents because of their ability to inhibit the growth of various types of cancer cell lines in culture (De Petrocellis et al., 1998; Ruiz et al., 1999; Sanchez et al., 1998, 2001) and in laboratory animals (Galve-Roperh et al., 2000).

In conclusion, the endocannabinoid system exerts a myriad of effects on tumor cell growth, progression, angiogenesis, and migration. With a notable few exceptions, targeting the endocannabinoid system with agents that activate cannabinoid receptors or increase the endogenous levels of AEA may prove to have therapeutic benefit in the treatment of various cancers. Further studies into the downstream consequences of AEA treatment are required and may illuminate other potential therapeutic targets.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2791688/

Cannabis-Linked Cell Receptor Might Help Prevent Colon Cancer – ABCNews

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“A cannabinoid receptor lying on the surface of cells may help suppress colorectal cancer, say U.S. researchers. When the receptor is turned off, tumor growth is switched on.

Cannabinoids are compounds related to the tetrahydrocannabinol (THC) found in the cannabis plant.

It’s already known that the receptor, CB1, plays a role in relieving pain and nausea, elevating mood and stimulating appetite by serving as a docking station for the cannabinoid group of signaling molecules. This study suggests that CB1 may offer a new path for cancer prevention or treatment.

“Potential application of cannabinoids as anti-tumor drugs is an exciting prospect, because cannabinoid agonists (synthetic molecules that mimic the action of natural molecules) are being evaluated now to treat the side effects of chemotherapy and radiation therapy,” DuBois said. “Turning CB1 back on and than treating with a cannabinoid agonist could provide a new approach to colorectal cancer treatment or prevention.””

http://abcnews.go.com/Health/Healthday/story?id=5496283&page=1

Chemopreventive effect of the non-psychotropic phytocannabinoid cannabidiol on experimental colon cancer.

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Abstract

“Colon cancer affects millions of individuals in Western countries. Cannabidiol, a safe and non-psychotropic ingredient of Cannabis sativa, exerts pharmacological actions (antioxidant and intestinal antinflammatory) and mechanisms (inhibition of endocannabinoid enzymatic degradation) potentially beneficial for colon carcinogenesis. Thus, we investigated its possible chemopreventive effect in the model of colon cancer induced by azoxymethane (AOM) in mice. AOM treatment was associated with aberrant crypt foci (ACF, preneoplastic lesions), polyps, and tumour formation, up-regulation of phospho-Akt, iNOS and COX-2 and down-regulation of caspase-3. Cannabidiol-reduced ACF, polyps and tumours and counteracted AOM-induced phospho-Akt and caspase-3 changes. In colorectal carcinoma cell lines, cannabidiol protected DNA from oxidative damage, increased endocannabinoid levels and reduced cell proliferation in a CB(1)-, TRPV1- and PPARγ-antagonists sensitive manner. It is concluded that cannabidiol exerts chemopreventive effect in vivo and reduces cell proliferation through multiple mechanisms.”

http://www.ncbi.nlm.nih.gov/pubmed/22231745

Cluster attacks responsive to recreational cannabis and dronabinol.

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Abstract

“Pharmacological preparations of cannabinoid compounds have a variety of therapeutic uses in medicine, including different pain syndromes, but have not been previously reported as beneficial for cluster headache. We present a patient with cluster headache who was refractory to multiple acute and preventive medications but successfully aborted his attacks with recreational marijuana use; subsequent use of dronabinol provided equally effective pain relief. The beneficial effect may be related to the high concentration of cannabinoid receptors in the hypothalamus, which has been implicated as a site of dysfunction in neuroimaging studies of patients with cluster headache.”

http://www.ncbi.nlm.nih.gov/pubmed/19220500

Cannabis for migraine treatment: the once and future prescription? An historical and scientific review.

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Abstract

“Cannabis, or Marijuana, has been used for centuries for both symptomatic and prophylactic treatment of migraine. It was highly esteemed as a headache remedy by the most prominent physicians of the age between 1874 and 1942, remaining part of the Western pharmacopoeia for this indication even into the mid-twentieth century. Current ethnobotanical and anecdotal references continue to refer to its efficacy for this malady, while biochemical studies of THC and anandamide have provided a scientific basis for such treatment. The author believes that controlled clinical trials of Cannabis in acute migraine treatment are warranted.”

http://www.ncbi.nlm.nih.gov/pubmed/9696453

 

Anandamide Is Able to Inhibit Trigeminal Neurons Using an in Vivo Model of Trigeminovascular-Mediated Nociception

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Abstract

“Arachidonylethanolamide (anandamide, AEA) is believed to be the endogenous ligand of the cannabinoid CB(1) and CB(2) receptors. CB(1) receptors have been found localized on fibers in the spinal trigeminal tract and spinal trigeminal nucleus caudalis. Known behavioral effects of anandamide are antinociception, catalepsy, hypothermia, and depression of motor activity, similar to Delta(9)-tetrahydocannanbinol, the psychoactive constituent of cannabis. It may be a possible therapeutic target for migraine. In this study, we looked at the possible role of the CB(1) receptor in the trigeminovascular system, using intravital microscopy to study the effects of anandamide against various vasodilator agents. Anandamide was able to inhibit dural blood vessel dilation brought about by electrical stimulation by 50%, calcitonin gene-related peptide (CGRP) by 30%, capsaicin by 45%, and nitric oxide by 40%. CGRP(8-37) was also able to attenuate nitric oxide (NO)-induced dilation by 50%. The anandamide inhibition was reversed by the CB(1) receptor antagonist AM251. Anandamide also reduced the blood pressure changes caused by CGRP injection, this effect was not reversed by AM251. It would seem that anandamide acts both presynaptically, to prevent CGRP release from trigeminal sensory fibers, and postsynaptically to inhibit the CGRP-induced NO release in the smooth muscle of dural arteries. CB(1) receptors seem to be involved in the NO/CGRP relationship that exists in causing headache and dural blood vessel dilation. It also seems that some of the blood pressure changes caused by anandamide are mediated by a noncannabinoid receptor, as AM251 was unable to reverse these effects. It can be suggested that anandamide is tonically released to play some form of modulatory role in the trigeminovascular system.

The known behavioral effects of anandamide are similar to that of Δ9-tetrahydrocannabinol, the psychoactive constituent of cannabis, being antinociception, catalepsy, hypothermia, and depression of motor activity (Dewey, 1986; Adams et al., 1998). Although there is a history of anecdotal evidence suggesting the use of cannabinoids is effective at reducing headache and providing other pain relief, its potential as an acute migraine treatment and even preventive has never been scientifically studied in animal studies or clinical trial (Russo, 1998). However, one anonymous standardized survey found that of those using cannabis medicinally, over 10% were using it to relieve headache or migraine (Schnelle et al., 1999). Although many aspects of the study are open to debate, such as the highly selected nature of patient group, it is nevertheless an interesting observation.”

http://jpet.aspetjournals.org/content/309/1/56.long

The periaqueductal gray contributes to bidirectional enhancement of antinociception between morphine and cannabinoids.

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“Co-administration of opioids and cannabinoids can enhance pain relief even when administered on different days. Repeated systemic administration of morphine has been shown to enhance the antinociceptive effect of tetrahydrocannbinol (THC) administered 12hours later, and repeated microinjection of the cannabinoid receptor agonist HU-210 into the ventrolateral periaqueductal gray (PAG) has been shown to enhance the antinociceptive effect of morphine administered one day later. The primary objective of the present study was to test the hypotheses that this cannabinoid/opioid interaction is bidirectional. Experiment 1 showed that microinjection of morphine into the ventrolateral PAG of male Sprague-Dawley rats twice daily for 2days enhanced the antinociceptive effect of HU-210 measured one day later. In Experiment 2, twice daily systemic injections of THC enhanced the antinociceptive effect of morphine administered one day later. These results complement the previously mentioned studies by showing that morphine and cannabinoid interactions are bidirectional and that the ventrolateral PAG plays an important role in this effect. In contrast to the PAG, repeated administration of HU-210 or the cannabinoid receptor agonist, WIN 55,212-2, into the RVM had a neurotoxic effect. Rats became ill following repeated cannabinoid administration whether given alone or with morphine. Presumably, this neurotoxic effect was caused by the high cannabinoid concentration following RVM microinjection because rats did not become ill following repeated systemic THC administration. These findings indicate that alternating opioid and cannabinoid treatment could produce a longer lasting and more potent analgesia than either compound given alone.”

http://www.ncbi.nlm.nih.gov/pubmed/23063785

Hallucinogens and cannabinoids for headache.

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“Most hallucinogens and cannabinoids fall into Federal Controlled Substances schedule 1, meaning they cannot be prescribed by practitioners, allegedly have no accepted medical use, and have a high abuse potential. The legal and regulatory status has inhibited clinical research on these substances such that there are no blinded studies from which to assess true efficacy. Despite such classification, hallucinogens and cannabinoids are used by patients with headache on occasion.

 Cannabinoids in particular have a long history of use for headache and migraine before prohibition and are still used by patients as a migraine abortive.

 Hallucinogens are being increasing used by cluster headache patients outside of physician recommendation mainly to abort a cluster period and to maintain quiescence for which there is considerable anecdotal success.”

http://www.ncbi.nlm.nih.gov/pubmed/23030539