Tag Archives: therapeutic

Cannabinoid CB1 antagonists possess antiparkinsonian efficacy only in rats with very severe nigral lesion in experimental parkinsonism.

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Abstract

“We have observed that systemic administration of cannabinoid CB1 antagonists exerts antiparkinsonian effects in rats with very severe nigral lesion (>95% cell loss), but not in rats with less severe lesion (85-95% cell loss). Local injections into denervated striatum and corresponding globus pallidus reduced parkinsonian asymmetry. Infusions into lesioned substantia nigra enhanced motor asymmetries, but this effect was absent after very severe nigral lesion. At the striatal level, CB1 antagonists act enhancing dopamine D1 receptor function and reducing D2 receptor function. Striatal dopaminergic denervation did not affect cannabinoid CB1 receptor coupling to G proteins. These results suggest that (i) systemic administration of CB1 antagonists in rats with severe nigral degeneration is ineffective because striatopallidal-mediated motor effects are antagonized by nigra-mediated activity, and (ii) CB1 antagonists exert antiparkinsonian effects after very severe nigral degeneration because nigra-mediated inhibition disappears. CB1 receptor antagonists that lack psychoactive effects might be of therapeutic value in the control of very advanced stage of Parkinson’s disease in humans.”

http://www.ncbi.nlm.nih.gov/pubmed/15755685

CB1 cannabinoid receptor signalling in Parkinson’s disease.

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Abstract

“Signalling at CB(1) cannabinoid receptors plays a key role in the control of movement in health and disease. In recent years, an increased understanding of the physiological role of transmission at CB(1) receptors throughout the basal ganglia circuitry has led to the identification of novel therapeutic approaches to both the symptoms of Parkinson’s disease and the side effects of current anti-parkinsonian therapies, especially L(3,4) dihydroxyphenylalamine (levodopa)-induced dyskinesia. Thus, because activation of basal ganglia CB(1) receptors can modulate neurotransmission and contribute to synaptic plasticity in a manner similar to that described in other brain regions, it also appears that endocannabinoids might modulate cell-cell signalling via effects on neurotransmitter re-uptake and postsynaptic actions mediating cross talk between multiple receptor types. Recent studies in animal models and in the clinic suggest that CB(1) receptor antagonists could prove useful in the treatment of parkinsonian symptoms and levodopa-induced dyskinesia, whereas CB(1) receptor agonists could have value in reducing levodopa-induced dyskinesia.”

http://www.ncbi.nlm.nih.gov/pubmed/12550742

Depression in Parkinson’s disease is related to a genetic polymorphism of the cannabinoid receptor gene (CNR1).

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Abstract

“Depression is a common symptom in Parkinson’s disease (PD) and it is present in up to 40% of the patients. The cause of depression in PD is thought to be related to disturbance of monoamine neurotransmission. The endogenous cannabinoid system mediates different brain processes that play a role in the control of behaviour and emotions. Cannabinoid function may be altered in neuropsychiatry diseases, directly or through interactions with monoamine, GABA and glutamate systems. For this reason, we have investigated whether there is a genetic risk factor for depression in PD linked to the polymorphisms of CB1 receptor gene. Depression was more frequent in patients with PD than in controls with osteoarthritis. The presence of depression did not correlate with the stage of the disease but it was more frequent in patients with pure akinetic syndrome than in those with tremoric or mixed type PD. The CB1 receptor gene polymorphism (AAT)n is considered to modify the transcription of the gene and, therefore, it may have functional relevance. We analysed the length of the polymorphic triplet (AAT)n of the gene that encodes CB1 (CNR1) receptor in 89 subjects (48 PD patients and 41 controls). In patients with PD, the presence of two long alleles, with more than 16 repeated AAT trinucleotides in the CNR1 gene, was associated with a reduced prevalence of depression (Fisher’s exact test: P=0.003). This association did not reach significant differences in the control group, but the number of control individuals with depression was too small to allow for statistical analysis. Since the alleles with long expansions may have functional impact in cannabinoid neurotransmission, our data suggest that the pharmacological manipulation of cannabinoid neurotransmission could open a new therapeutic approach for the treatment of depression in PD and possibly in other conditions.”

http://www.ncbi.nlm.nih.gov/pubmed/15668727

Smoked cannabis proven effective in treating neuropathic pain.

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UC San Diego Health

“Smoked cannabis eased pain induced in healthy volunteers, according to a study by researchers at the University of California, San Diego (UCSD) Center for Medical Cannabis Research (CMCR.) However, the researchers found that less may be more.”

“The results, showing a medium-dose (4% THC by weight) of cannabis to be an effective analgesic, converged with results from the CMCR’s first published study, a paper by UCSF researcher Donald Abrams, M.D. published in the journal Neurology in February 2007. In that randomized placebo-controlled trial, patients smoking the same dose of cannabis experienced a 34% reduction in HIV-associated sensory neuropathy pain—twice the rate experienced by patients receiving a placebo.”

““This study helps to build a case that cannabis does have therapeutic value at a medium-dose level,” said Grant. “It also suggests that higher doses aren’t necessarily better in certain situations – something also observed with other medications, such as antidepressants.””

Read more: http://phys.org/news112456382.html

“Smoked Cannabis Proven Effective In Treating Neuropathic Pain”  https://www.sciencedaily.com/releases/2007/10/071024141745.htm

“Smoked cannabis proven effective in treating neuropathic pain”  https://medicalxpress.com/news/2007-10-cannabis-proven-effective-neuropathic-pain.html

“Smoked Cannabis Proven Effective in Treating Neuropathic Pain”  https://health.ucsd.edu/news/2007/pages/10-24-medical-cannabis.aspx

Role of cannabinoids in the management of neuropathic pain.

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Abstract

“The treatment of pain, particularly neuropathic pain, is one of the therapeutic applications of cannabis and cannabinoids that is currently under investigation and that stimulates interest among clinicians and basic researchers. Animal pain models, including models of acute, antinociceptive, inflammatory and neuropathic pain, have demonstrated the antinociceptive efficacy of cannabinoids without causing serious alterations in animal behaviour. These data, together with the historic and current empiric use of cannabinoids, support the interest in the analysis of their effectiveness in treating neuropathic pain. The evaluation of controlled trials that focus on the effect of cannabinoids on neuropathic pain reveals that this class of drugs is able to significantly reduce pain perception. Nevertheless, this effect is generally weak and clinical relevance remains under evaluation. Moreover, there is a lack of controlled trials and, in particular, comparisons with other drugs generally used in the treatment of neuropathic pain. Despite the fact that further research is required to achieve a definitive assessment, current data obtained from basic research and from analysis of the available controlled trials indicate that cannabinoids can be accepted as a useful option in the treatment of neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/18601303

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

Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review.

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“Spasticity, an involuntary increase in muscle tone or rapid muscle contractions, is one of the more common and distressing symptoms of multiple sclerosis (MS). Medicinal treatment may reduce spasticity, but may also be ineffective, difficult to obtain, or associated with intolerable side effects. Cannabis, a psychotropic drug known for its analgesic properties, also has a long history as an effective and tolerable treatment for spasticity]. Demographic evidence has shown that many people with MS use cannabis for symptom management.

Clinical studies, animal models, and anecdotal reports have suggested that cannabis may be an effective treatment of MS spasticity. The antispastic effect of cannabis has been supported through a demonstration of the inhibitory properties in exogenous agonists for cannabis receptors found in the CNS. Early clinical trials reporting the efficacy and safety of cannabis use in MS have focused on the effects of Δ9-tetrahydrocannabinol (THC). Although these clinical studies reported a therapeutic benefit for MS symptoms, there were concerns of potential intoxication and other side effects of cannabis-based treatment. Another clinical study using a cannabidiol (CBD) extract documented a reduction in spasticity-related pain but not in spasticity..

More recent combination therapies using whole plant extracts of both THC and CBD have been introduced and there is evidence that CBD, which is not psychotropic, may reduce THC levels in the brain and attenuate its psychotropic side effects. Such therapies may potentially provide a tolerable yet effective treatment for MS symptoms. A number of recent studies have investigated the potential efficacy and safety of whole plant extracts of THC and CBD. One of the first large-scale studies of cannabis treatment for MS-related spasticity compared whole plant cannabis extracts with THC and a placebo, and found mixed evidence for the therapeutic benefit of spasticity in MS. A recent review that included a number of these recent studies provided additional support for the benefit of cannabinoids in MS-related spasticity but called for further study into long-term treatment and side effects. A systematic evaluation of recent research had not previously been conducted, and was needed in order to provide organized evidence of cannabinoid treatments and direction for future clinical studies. We therefore systematically reviewed studies that used a combination extract of THC and CBD for the treatment of spasticity.

We found evidence that combined THC and CBD extracts may provide therapeutic benefit for MS spasticity symptoms…

Finally, there is evidence that cannabinoids may provide neuroprotective and anti-inflammatory benefits in MS. Neuroinflammation, found in autoimmune diseases such as MS, has been shown to be reduced by cannabinoids through the regulation of cytokine levels in microglial cells. The therapeutic potential of cannabinoids in MS is therefore comprehensive and should be given considerable attention.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2793241/

Increased expressions of cannabinoid receptor-1 and transient receptor potential vanilloid-1 in human prostate carcinoma.

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“PURPOSE:

Recently, functional cannabinoid receptor-1 (CB1) and vanilloid receptor-1 (TRPV1) have been described in human prostate and prostate cancer-derived cell lines where the activation of the receptors resulted in inhibition of cellular growth. We, however, lack the description of the expression of these molecules in human prostate cancer (PCC) and in benign prostate hyperplasia (BPH).

RESULTS:

CB1 was identified in epithelial and smooth muscle cells types of the human prostate, whereas TRPV1 was exclusively localized to the mucosal cells. We also found that the expression of CB1 and TRPV1 (both at the protein and mRNA levels) were significantly up-regulated in PCC. However, while the increased expression of TRPV1 showed a proper correlation with increasing PCC tumor grades, such phenomenon was not observed with CB1. In addition, we also measured markedly elevated CB1 levels in BPH tissues whilst the expression of TRPV1 was not altered when compared to healthy control prostate.

CONCLUSIONS:

Our findings strongly argue for that (1) the CB1 and TRPV1 molecules as well as their ligands may indeed possess a promising future role in the treatment of PCC; (2) TRPV1 may also serve as a prognostic factor in PCC; and (3) CB1 may act as a potential target molecule in the therapeutic management of BPH.”

http://www.ncbi.nlm.nih.gov/pubmed/18830626

The role of cannabinoids in prostate cancer: Basic science perspective and potential clinical applications.

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“Prostate cancer is a global public health problem, and it is the most common cancer in American men and the second cause for cancer-related death. Experimental evidence shows that prostate tissue possesses cannabinoid receptors and their stimulation results in anti-androgenic effects.”

“Cannabis is a bushy plant with palmate leaves and clusters of small green flowers, and it grows wild in regions of tropical weather and can attain up to 3 m height. The genus Cannabis is complemented by sativa which translates to useful. Cannabis has indeed been used throughout history for a variety of purposes, including the production of fiber for paper and textile manufacture. However, its current popularity lies in its use as a recreational drug with psychoactive properties. The plant contains many chemical compounds that have different pharmacological properties, varying in quantity and quality depending on the strain, culture, and storage conditions.”

“The frequently held view of cannabis and its related products as drugs of abuse have slowed progress in the development of studies designed to take advantage of the properties of cannabinoid derivatives for therapeutic purposes…”

“Delta-9-THC is the substance with the greatest psychoactive potency of the natural cannabinoids and exhibits the greatest analgesic activity. Cannabidiol (CBD), another major constituent of the Cannabis sativa plant, has the same therapeutic effects of THC (analgesic, anti-inflammatory, and others), but with a different pharmacologic profile…”

“It is our conclusion that it would be of interest to conduct clinical trials involving medicinal cannabis or other cannabinoid agonists, comparing clinical markers such as PSA with controls, especially in men with bone metastatic prostate cancer, whom would not only benefit from the possible anti-androgenic effects of cannabinoids but also from analgesia of bone pain, improving quality of life, while reducing narcotic consumption and preventing opioid dependence.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339795/

Cannabinoid Receptor as a Novel Target for the Treatment of Prostate Cancer

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“Because prostate cancer has become the most common cancer diagnosed in men, developing novel targets and mechanism-based agents for its treatment has become a challenging issue. In recent years cannabinoids, the active components of Cannabis sativa Linnaeus (marijuana) and their derivatives have drawn renewed attention because of their diverse pharmacologic activities such as cell growth inhibition, anti-inflammatory effects, and tumor regression . Cannabinoids have been shown to induce apoptosis in gliomas, PC-12 pheochromocytoma, CHP 100 neuroblastoma, and hippocampal neurons in vitro, and most interestingly, regression of C6-cell gliomas in vivo. Further interest in cannabinoid research came from the discovery of specific cannabinoid systems and the cloning of specific cannabinoid receptors. These diversified effects of cannabinoids are now known to be mediated by the activation of specific G protein-coupled receptors that are normally bound by a family of endogenous ligands, the endocannabinoids. Two different cannabinoid receptors have been characterized and cloned from mammalian tissues: the “central” CB1 receptor, and the “peripheral” CB2 receptor.”

“In the present study, we show for the first time that expression levels of both cannabinoid receptors, CB1 and CB2, are higher in human prostate cancer cells than in normal cells. Importantly, we also show that WIN-55,212-2 (CB1/CB2 agonist) treatment with androgen-responsive LNCaP cells results in a dose- and time-dependent inhibition of cell growth with a concomitant induction of apoptosis, decrease in protein and mRNA expression of androgen receptor and prostate-specific antigen (PSA), decrease in secreted PSA levels, protein expression of proliferating cell nuclear antigen (PCNA), and vascular endothelial growth factor (VEGF). We suggest that cannabinoid receptor agonists may be useful in the treatment of human prostate cancer.”

“…non–habit-forming cannabinoid receptor agonists could be developed as novel therapeutic agents for the treatment of prostate cancer.”

“We conclude that cannabinoids should be considered as agents for the management of prostate cancer.”

.http://cancerres.aacrjournals.org/content/65/5/1635.long