Effects of cannabinoids on lithium-induced conditioned rejection reactions in a rat model of nausea.

“Marijuana has been reported to suppress nausea produced by chemotherapy treatment in human cancer patients.

… there is abundant evidence that cannabinoid agonists attenuate vomiting in emetic species…

The present experiments evaluated the potential of low doses of the cannabinoid agonists, delta-9-tetrahydrocannabinol (THC; 0.5 mg/kg, i.p.), and HU-210 (0.001 mg/kg and 0.01 mg/kg, i.p.), and the CB(1) antagonist SR-141716A in modulating the establishment and the expression of lithium-induced conditioned rejection reactions in rats.

These results indicate that the establishment and the expression of lithium-induced conditioned rejection reactions are suppressed by pretreatment with cannabinoid agents.”

http://www.ncbi.nlm.nih.gov/pubmed/12528012

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

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

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“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/

Therapeutic potential of cannabis in pain medicine†

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.

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“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/

Modulation of HIVGP120 Antigen-Specific Immune Responses In Vivo by Δ9-Tetrahydrocannabinol.

“Approximately 25 % of HIV patients use marijuana for its putative therapeutic benefit…

Previously, a surrogate in vitro mouse model was established, which induced CD8+ T cell proliferation and gp120-specific IFNγ production. ∆9-Tetrahydrocannabinol (THC), the predominant psychoactive compound in marijuana, suppressed or enhanced the responses depending on the magnitude of cellular activation.

The purpose of the current study was to investigate whether THC produced similar effects in vivo and therefore a mouse model to induce HIVgp120-specific immune responses was established…

Collectively, our findings demonstrate that under certain conditions, THC enhances HIV antigen-specific immune responses, which occurs through CB1/CB2-dependent and -independent mechanisms.”

http://www.ncbi.nlm.nih.gov/pubmed/25900076

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

Cannabinoids Inhibit T-cells via Cannabinoid Receptor 2 in an in vitro Assay for Graft Rejection, the Mixed Lymphocyte Reaction

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“Cannabinoids are known to have anti-inflammatory and immunomodulatory properties.

Cannabinoid receptor 2 (CB2) is expressed mainly on leukocytes and is the receptor implicated in mediating many of the effects of cannabinoids on immune processes.

This study tested the capacity of Δ9-tetrahydrocannabinol (Δ9-THC) and of two CB2-selective agonists to inhibit the murine Mixed Lymphocyte Reaction (MLR), an in vitro correlate of graft rejection following skin and organ transplantation. Both CB2-selective agonists and Δ9-THC significantly suppressed the MLR in a dose dependent fashion…

Together, these data support the potential of this class of compounds as useful therapies to prolong graft survival in transplant patients.

Cannabinoids were reported to have effects on immune responses as early as the 1970s, but the basis for this activity was not understood until the cannabinoid receptors were cloned

Ideally, the anatomically disparate expression of CB1 and CB2 would allow for the use of compounds selective for CB2, and thus eliminate the unwanted psychoactive effects from CB1 activation, while maintaining the anti-inflammatory and immunosuppressive properties.

CB2-selective cannabinoids have been proposed as possible candidates to block graft rejection.

The results presented in this paper show that Δ9-THC, a mixed CB1/CB2 agonist, and two CB2-selective agonists can inhibit the Mixed Lymphocyte Reaction (MLR), an in vitro correlate of organ and skin graft rejection.”

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864984/

Promising cannabinoid-based therapies for Parkinson’s disease: motor symptoms to neuroprotection.

“Parkinson’s disease (PD) is a slow insidious neurological disorder characterized by a loss of dopaminergic neurons in the midbrain. Although several recent preclinical advances have proposed to treat PD, there is hardly any clinically proved new therapeutic for its cure.

Increasing evidence suggests a prominent modulatory function of the cannabinoid signaling system in the basal ganglia. Hence, use of cannabinoids as a new therapeutic target has been recommended as a promising therapy for PD.

The elements of the endocannabinoid system are highly expressed in the neural circuit of basal ganglia wherein they bidirectionally interact with dopaminergic, glutamatergic, and GABAergic signaling systems.

As the cannabinoid signaling system undergoes a biphasic pattern of change during progression of PD, it explains the motor inhibition typically observed in patients with PD.

Cannabinoid agonists such as WIN-55,212-2 have been demonstrated experimentally as neuroprotective agents in PD, with respect to their ability to suppress excitotoxicity, glial activation, and oxidative injury that causes degeneration of dopaminergic neurons.

Additional benefits provided by cannabinoid related compounds including CE-178253, oleoylethanolamide, nabilone and HU-210 have been reported to possess efficacy against bradykinesia and levodopa-induced dyskinesia in PD.

Despite promising preclinical studies for PD, use of cannabinoids has not been studied extensively at the clinical level. In this review, we reassess the existing evidence suggesting involvement of the endocannabinoid system in the cause, symptomatology, and treatment of PD. We will try to identify future threads of research that will help in the understanding of the potential therapeutic benefits of the cannabinoid system for treating PD.”

http://www.ncbi.nlm.nih.gov/pubmed/25888232

“To conclude, development of safe, effective cannabis-based medicines targeting different mechanisms may have a significant impact in PD therapy.”

Full-text: http://www.molecularneurodegeneration.com/content/10/1/17

http://www.thctotalhealthcare.com/category/parkinsons-disease/

Effects of Cannabinoids on T-cell Function and Resistance to Infection.

“This review examines the effects of cannabinoids on immune function, with a focus on effects on T-cells, as well as on resistance to infection. The paper considers the immune modulating capacity of marijuana, of ∆9-THC extracted from the marijuana plant, and synthetic cannabinoids…

The overall conclusion of the studies discussed in this review is that cannabinoids that bind to the CB2 receptor, including ∆9-THC and CB2 selective agonists are immunosuppressive.

The studies provide objective evidence for potentially beneficial effects of marijuana and ∆9-THC on the immune system in conditions where it is desirable to dampen immune responses.

An emerging area of investigation that is reviewed is evidence to support the conclusion that CB2 selective agonists are a new class of immunosuppressive and anti-inflammatory compounds that may have exceptional beneficial effects in a variety of conditions, such as autoimmune diseases and graft rejection, where it is desirable to dampen the immune response without psychoactive effects.”

http://www.ncbi.nlm.nih.gov/pubmed/25876735

http://www.thctotalhealthcare.com/category/autoimmune-disease/

Cannabis and cardiotoxicity.

“Cannabis is the most commonly consumed illicit drug… Despite the drug’s extreme popularity, reports of cannabis-related stroke and myocardial infarction are so rare as to still be reportable… The observation that cardiotoxicity has never been reported in cancer patients taking dronabinol, the synthetic form of THC, tends to suggest that animal studies may have overstated the cardiovascular risk,” http://www.ncbi.nlm.nih.gov/pubmed/25868498

http://www.thctotalhealthcare.com/category/cardiovascular-disease/

Sequence heterogeneity of cannabidiolic- and tetrahydrocannabinolic acid-synthase in Cannabis sativa L. and its relationship with chemical phenotype.

“Sequence variants of THCA- and CBDA-synthases were isolated from different Cannabis sativa L. strains expressing various wild-type and mutant chemical phenotypes (chemotypes). Expressed and complete sequences were obtained from mature inflorescences. Each strain was shown to have a different specificity and/or ability to convert the precursor CBGA into CBDA and/or THCA type products. The comparison of the expressed sequences led to the identification of different mutations, all of them due to SNPs. These SNPs were found to relate to the cannabinoid composition of the inflorescence at maturity and are therefore proposed to have a functional significance. The amount of variation was found to be higher within the CBDAS sequence family than in the THCAS family, suggesting a more recent evolution of THCA-forming enzymes from the CBDAS group. We therefore consider CBDAS as the ancestral type of these synthases.”

http://www.ncbi.nlm.nih.gov/pubmed/25865737