Cannabidiol, a non-psychoactive component of cannabis and its synthetic dimethylheptyl homolog suppress nausea in an experimental model with rats.

Posted on April 27, 2015 by David

“Rats display conditioned rejection reactions during an oral infusion of a flavor previously paired with an emetic drug; considerable evidence indicates that these rejection reactions reflect nausea.

Here we report that cannabidiol, a major non-psychoactive cannabinoid found in marijuana and its synthetic dimethylheptyl homolog interfere with nausea elicited by lithium chloride and with conditioned nausea elicited by a flavor paired with lithium chloride.

These results suggest that cannabinoids without psychoactive side-effects may have therapeutic value in the treatment of chemotherapy-induced nausea.”

http://www.ncbi.nlm.nih.gov/pubmed/11973447

http://www.thctotalhealthcare.com/category/nauseavomiting/

The endocannabinoid system as a target for the treatment of neurodegenerative disease.

Posted on April 27, 2015 by David

“The Cannabis sativa plant has been exploited for medicinal, agricultural and spiritual purposes in diverse cultures over thousands of years.

Cannabis has been used recreationally for its psychotropic properties, while effects such as stimulation of appetite, analgesia and anti-emesis have lead to the medicinal application of cannabis.

Indeed, reports of medicinal efficacy of cannabis can been traced back as far as 2700 BC, and even at that time reports also suggested a neuroprotective effect of the cultivar.

…alterations in the endocannabinoid system have been extensively investigated in a range of neurodegenerative disorders.

In this review we examine the evidence implicating the endocannabinoid system in the cause, symptomatology or treatment of neurodegenerative disease. We examine data from human patients and compare and contrast this with evidence from animal models of these diseases. On the basis of this evidence we discuss the likely efficacy of endocannabinoid-based therapies in each disease context.

There has been anecdotal and preliminary scientific evidence of cannabis affording symptomatic relief in diverse neurodegenerative disorders. These include multiple sclerosis, Huntington’s, Parkinson’s and Alzheimer’s diseases, and amyotrophic lateral sclerosis.

This evidence implied that hypofunction or dysregulation of the endocannabinoid system may be responsible for some of the symptomatology of these diseases.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931550/

Cannabidiol in medicine: a review of its therapeutic potential in CNS disorders.

Posted on April 27, 2015 by David

“Cannabidiol (CBD) is the main non-psychotropic component of the glandular hairs of Cannabis sativa.

It displays a plethora of actions including anticonvulsive, sedative, hypnotic, antipsychotic, antiinflammatory and neuroprotective properties.

However, it is well established that CBD produces its biological effects without exerting significant intrinsic activity upon cannabinoid receptors.

For this reason, CBD lacks the unwanted psychotropic effects characteristic of marijuana derivatives, so representing one of the bioactive constituents of Cannabis sativa with the highest potential for therapeutic use.

The present review reports the pharmacological profile of CBD and summarizes results from preclinical and clinical studies utilizing CBD, alone or in combination with other phytocannabinoids, for the treatment of a number of CNS disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/18844286

Therapeutic potential of cannabis in pain medicine†

Posted on April 27, 2015 by David

BJA

“Cannabis has been of medicinal and social significance for millennia.

It is obtained from Cannabis sativa and the plant’s name reflects its ancient use—cannabis may represent a compound of Sanskrit and Hebrew words meaning ‘fragrant cane’, while sativa is Latin for cultivated.

Cannabis is also known as hemp.

Marijuana describes the dried cannabis flowers and leaves which are smoked, while hashish refers to blocks of cannabis resin which can be eaten.

Advances in cannabis research have paralleled developments in opioid pharmacology whereby a psychoactive plant extract has elucidated novel endogenous signalling systems with therapeutic significance.

Cannabinoids (CBs) are chemical compounds derived from cannabis.

This review discusses the basic science and clinical aspects of CB pharmacology with a focus on pain medicine.

Advances in cannabis research have ensured a future for these analgesic molecules which have been used since antiquity.”

http://bja.oxfordjournals.org/content/101/1/59.long

http://www.thctotalhealthcare.com/category/pain-2/

Evaluation of prevalent phytocannabinoids in the acetic acid model of visceral nociception.

Posted on April 27, 2015 by David

“Cannabis has been used for thousands of years as a therapeutic agent for pain relief, as well as for recreational purposes.

Delta-9-Tetrahydrocannabinol (Δ9-THC)… produces antinociceptive effects in a wide range of preclinical assays of pain.

Considerable preclinical research has demonstrated the efficacy of Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the primary psychoactive constituent of Cannabis sativa, in a wide variety of animal models of pain, but few studies have examined other phytocannabinoids.

Indeed, other plant-derived cannabinoids, including cannabidiol (CBD), cannabinol (CBN), and cannabichromene (CBC) elicit antinociceptive effects in some assays. In contrast, tetrahydrocannabivarin (THCV), another component of cannabis, antagonizes the pharmacological effects of Delta(9)-THC.

These results suggest that various constituents of this plant may interact in a complex manner to modulate pain.

The primary purpose of the present study was to assess the antinociceptive effects of these other prevalent phytocannabinoids in the acetic acid stretching test, a rodent visceral pain model…

Importantly, the antinociceptive effects of Delta(9)-THC and CBN occurred at lower doses than those necessary to produce locomotor suppression, suggesting motor dysfunction did not account for the decreases in acetic acid-induced abdominal stretching.

These data raise the intriguing possibility that other constituents of cannabis can be used to modify the pharmacological effects of Delta(9)-THC by either eliciting antinociceptive effects (i.e., CBN) or antagonizing (i.e., THCV) the actions of Delta(9)-THC.

The results obtained in the present study are consistent with the view that Δ9-THC is the major phytocannabinoid present in marijuana that produces antinociception in the acetic acid abdominal stretching test.

…these results suggest that there is potential to develop medications containing various concentrations of specific phytocannabinoids to optimize therapeutic effects (e.g., antinociception) and minimize psychomimetic effects.

In sum, the results of the present study further support the notion that Δ9-THC is the predominant constituent of marijuana that is responsible for eliciting antinociceptive effects and indicate that CB1 receptors play a predominant role in mediating these effects.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2765124/

http://www.thctotalhealthcare.com/category/pain-2/

Responsible and controlled use: Older cannabis users and harm reduction.

Posted on April 26, 2015 by David

“Cannabis use is becoming more accepted in mainstream society. In this paper, we use Zinberg’s classic theoretical framework of drug, set, and setting to elucidate how older adult cannabis users managed health, social and legal risks in a context of normalized cannabis use…

Interviewees made harm reduction choices based on preferred cannabis derivatives and routes of administration, as well as why, when, where, and with whom to use. Most interviewees minimized cannabis-related harms so they could maintain social functioning in their everyday lives. Responsible and controlled use was described as moderation of quantity and frequency of cannabis used, using in appropriate settings, and respect for non-users. Users contributed to the normalization of cannabis use through normification.

Participants followed rituals or cultural practices, characterized by sanctions that helped define “normal” or “acceptable” cannabis use. Users contributed to cannabis normalization through their harm reduction methods.

These cultural practices may prove to be more effective than formal legal prohibitions in reducing cannabis-related harms.

Findings also suggest that users with access to a regulated market (medical cannabis dispensaries) were better equipped to practice harm reduction.

More research is needed on both cannabis culture and alternative routes of administration as harm reduction methods.”

http://www.ncbi.nlm.nih.gov/pubmed/25911027

Inhibition of FAAH reduces nitroglycerin-induced migraine-like pain and trigeminal neuronal hyperactivity in mice.

Posted on April 26, 2015 by David

“There is evidence to suggest that a dysregulation of endocannabinoid signaling may contribute to the etiology and pathophysiology of migraine.

Thus, patients suffering from chronic migraine or medication overuse headache showed alterations in the activity of the arachidonoylethanolamide (AEA) degrading enzyme fatty acid amide hydrolase (FAAH) and a specific AEA membrane transporter, alongside with changes in AEA levels.

The precise role of different endocannabinoid system components is, however, not clear. We have therefore investigated mice with a genetic deletion of the two main cannabinoid receptors CB1 and CB2, or the main endocannabinoid degrading enzymes, FAAH and monoacylglycerol lipase (MAGL), which degrades 2-arachidonoylglycerol (2-AG), in a nitroglycerine-induced animal model of migraine.

The effects of the genetic deletion of pharmacological blockade of FAAH are mediated by CB1 receptors, because they were completely disrupted with the CB1 antagonist rimonabant.

These results identify FAAH as a target for migraine pharmacotherapy.”

http://www.ncbi.nlm.nih.gov/pubmed/25910421

http://www.thctotalhealthcare.com/category/headachemigraine/

The complex modulation of lysosomal degradation pathways by cannabinoid receptor 1 and 2.

Posted on April 25, 2015 by David

“The two main receptors of the endocannabinoid system, cannabinoid receptor 1 (CB1R) and 2 (CB2R) were described in the early 1990s. Since then, different physiological functions have been revealed that are linked to the activity of these two G-protein-coupled receptors.

CB1R and CB2R activity influences signal Cascades, which are known to play a role in the regulation of the cellular “self-digestion” process called autophagy. A variety of these signaling pathways are integrated by the mammalian target of rapamycin complex 1 (mTORC1) that acts as an inhibitor of autophagy. Others, like AMP-activated protein kinase dependent signaling pathway, are able to bypass mTORC1 to modulate the autophagic activity directly.

In the recent years, several scientific reports demonstrate an involvement of CB1R and CB2R signaling in the control of the autophagic activity in different paradigms.

In this review, we summarize the recent literature on this topic, which is in part contradictory and therefore, it is of great importance to illuminate the results of the single reports in the physiological context of the model systems used in these studies.

Utilizing CB1R and CB2R as pharmacological targets to modulate the autophagic activity is a promising treatment strategy for the treatment of different patho-physiological conditions and disease.”

http://www.ncbi.nlm.nih.gov/pubmed/25908257

CB1 Knockout Mice Unveil Sustained CB2-Mediated Anti-Allodynic Effects of the Mixed CB1/CB2 Agonist CP55,940 in a Mouse Model of Paclitaxel-Induced Neuropathic Pain.

Posted on April 24, 2015 by David

“Cannabinoids suppress neuropathic pain through activation of cannabinoid CB1 and/or CB2 receptors. However, unwanted CB1-mediated cannabimimetic effects limit clinical use…

Our results using the mixed CB1/CB2 agonist document that CB1 and CB2 receptor activations produce mechanistically distinct suppression of neuropathic pain.

Our study highlights the therapeutic potential of targeting cannabinoid CB2 receptors to bypass unwanted central effects associated with CB1receptor activation.”

http://www.ncbi.nlm.nih.gov/pubmed/25904556

http://www.thctotalhealthcare.com/category/neuropathic-pain/

Cannabidiol stimulates Aml-1a-dependent glial differentiation and inhibits glioma stem-like cells proliferation by inducing autophagy in a TRPV2-dependent manner.

Posted on April 24, 2015 by David

“Glioma stem-like cells (GSCs) correspond to a tumor cell subpopulation, involved in glioblastoma multiforme (GBM) tumor initiation and acquired chemoresistance. Currently, drug-induced differentiation is considered as a promising approach to eradicate this tumor-driving cell population.

Recently, the effect of cannabinoids (CBs) in promoting glial differentiation and inhibiting gliomagenesis has been evidenced. Herein, we demonstrated that cannabidiol (CBD) by activating Transient Receptor Potential Vanilloid-2 (TRPV2) triggers GSCs differentiation activating the autophagic process and inhibits GSCs proliferation and clonogenic capability.

Above all, CBD and carmustine (BCNU) in combination overcome the high resistance of GSCs to BCNU treatment, by inducing apoptotic cell death…

Altogether, these results support a novel mechanism by which CBD inducing TRPV2-dependent autophagic process stimulates Aml-1a-dependent GSCs differentiation, abrogating the BCNU chemoresistance in GSCs.”

http://www.ncbi.nlm.nih.gov/pubmed/25903924

http://www.thctotalhealthcare.com/category/gllomas/