Marijuana-Like Compounds May Aid Array Of Debiliatiing Conditions Ranging From Parkinson’s Disease To Pain

“Oct. 27, 2004 — No longer a pipe dream, new animal research now indicates that marijuana-like compounds can aid a bevy of debilitating conditions, ranging from brain disorders such as amyotrophic lateral sclerosis (ALS) and Parkinson’s disease, to pain and obesity.

Research from California Pacific Medical Center in San Francisco points to the promise of marijuana-like treatments for those with the fatal brain disorder ALS, also known as Lou Gehrig’s disease.

“Our research indicates that select marijuana compounds, including THC, significantly slow the disease process and extend the life of mice with ALS,” says study author Mary Abood, PhD.

The study extends earlier work from Abood’s group that found that THC also can alleviate some ALS symptoms, like muscle spasms, in patients.

ALS wreaks its havoc by harming nerve cells that control muscles. As a consequence of the damage, an estimated 5,000 Americans afflicted annually experience progressive muscle weakness that can hinder movement, speech, even swallowing and breathing. New treatments for ALS are desperately needed…

“For the first time, our research shows the neuroprotective value of marijuana-like compounds in a well-established animal model of Parkinson’s disease,” says study author Andrea Giuffrida, PhD, of the University of Texas Health Science Center in San Antonio.

Parkinson’s afflicts some 1 million Americans. Symptoms include slowness of movement, muscle stiffness, and shaky tremors, which can harm a person’s ability to walk, talk, write, and eat. This havoc results from the death or injury of brain cells that produce the chemical dopamine.

“There are therapies that can help replenish depleted levels of dopamine and provide symptomatic relief, but none can reverse, prevent, or delay the progression of Parkinson’s disease,” says Giuffrida. “Our research shows that marijuana-like compounds may be able to answer this need.””

Read more: http://www.sciencedaily.com/releases/2004/10/041027102621.htm

 

Effects of cannabinoids Δ(9)-tetrahydrocannabinol, Δ(9)-tetrahydrocannabinolic acid and cannabidiol in MPP+ affected murine mesencephalic cultures.

Abstract

“Cannabinoids derived from Cannabis sativa demonstrate neuroprotective properties in various cellular and animal models. Mitochondrial impairment and consecutive oxidative stress appear to be major molecular mechanisms of neurodegeneration. Therefore we studied some major cannabinoids, i.e. delta-9-tetrahydrocannabinolic acid (THCA), delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in mice mesencephalic cultures for their protective capacities against 1-methyl-4-phenyl pyridinium (MPP(+)) toxicity. MPP(+) is an established model compound in the research of parkinsonism that acts as a complex I inhibitor of the mitochondrial respiratory chain, resulting in excessive radical formation and cell degeneration. MPP(+) (10 μM) was administered for 48 h at the 9th DIV with or without concomitant cannabinoid treatment at concentrations ranging from 0.01 to 10 μM. All cannabinoids exhibited in vitro antioxidative action ranging from 669 ± 11.1 (THC), 16 ± 3.2 (THCA) to 356 ± 29.5 (CBD) μg Trolox (a vitamin E derivative)/mg substance in the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay. Cannabinoids were without effect on the morphology of dopaminergic cells stained by tyrosine hydroxylase (TH) immunoreaction. THC caused a dose-dependent increase of cell count up to 17.3% at 10 μM, whereas CBD only had an effect at highest concentrations (decrease of cell count by 10.1-20% at concentrations of 0.01-10 μM). It influenced the viability of the TH immunoreactive neurons significantly, whereas THCA exerts no influence on dopaminergic cell count. Exposure of cultures to 10 μM of MPP(+) for 48 h significantly decreased the number of TH immunoreactive neurons by 44.7%, and shrunken cell bodies and reduced neurite lengths could be observed. Concomitant treatment of cultures with cannabinoids rescued dopaminergic cells. Compared to MPP(+) treated cultures, THC counteracted toxic effects in a dose-dependent manner. THCA and CBD treatment at a concentration of 10 μM lead to significantly increased cell counts to 123% and 117%, respectively. Even though no significant preservation or recovery of neurite outgrowth to control values could be observed, our data show that cannabinoids THC and THCA protect dopaminergic neurons against MPP(+) induced cell death.”

http://www.ncbi.nlm.nih.gov/pubmed/22571976

Cannabinoid receptor agonist protects cultured dopaminergic neurons from the death by the proteasomal dysfunction.

“Cannabinoids (CBs) from the Cannabis sativa L. plant, including tetrahydrocannabinol, the principal psychoactive component of marijuana, produce euphoria and relaxation and also impair motor coordination, perception of time, and short-term memory. The principal actions of CBs are mediated by activation of their cognate receptors on presynaptic nerve ends. Various types of cannabinoid receptors, including the orphan G-protein coupled receptors CB1 and CB2, are found in blood vessels, the central nervous system, and immune cells. While CB1 is expressed abundantly in several areas in the brain as well as in peripheral tissues, CB2 is primarily expressed in the immune system, although it was recently detected at low levels in peripheral nerve endings, microglial cells, and astrocytes, as well as in the cerebellum and brain stem. CB1 receptor activation is involved in the control of neural cell fate and mediates neuroprotectivity in different in vivo models of brain injury, including excitotoxicity and ischemia.

In recent years, the capacity of CBs to effect neuroprotection and neurotoxicity has received increasing attention. Evidence of possible neuroprotective effects has accumulated in vitro from models of neurodegenerative diseases, including Alzheimer’s and Parkinson’s diseases and multiple sclerosis, as well as from in vivo clinical trial data. These compounds are also able to decrease inflammation by acting on glial cells that influence neuronal survival. The molecular mechanisms underlying cannabinoid-mediated neuroprotection are still poorly understood, but may include the direct activation of neuronal survival signaling pathways through cannabinoid receptors or indirect effects mediated by microglial CB2-receptor stimulation.

Here, we investigated the neuroprotective function of a synthetic cannabinoid-receptor agonist (WIN55.212.2)… These results indicate that WIN55.212.2 may be a candidate for treatment of neurodegenerative diseases, including Parkinson’s disease.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145842/

Cannabinoids reduce levodopa-induced dyskinesia in Parkinson’s disease: a pilot study.

Abstract

“The lateral segment of the globus pallidus (GPl) is thought to be overactive in levodopa-induced dyskinesia in PD. Stimulation of cannabinoid receptors in the GPl reduces gamma-aminobutyric acid (GABA) reuptake and enhances GABA transmission and may thus alleviate dyskinesia. In a randomized, double-blind, placebo-controlled, crossover trial (n = 7), the authors demonstrate that the cannabinoid receptor agonist nabilone significantly reduces levodopa-induced dyskinesia in PD.”

http://www.ncbi.nlm.nih.gov/pubmed/11739835

Smoked cannabis proven effective in treating neuropathic pain.

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

Smoked Medical Cannabis May Be Beneficial as Treatment for Chronic Neuropathic Pain, Study Suggests.

“Medicinal marijuana. A new study provides evidence that cannabis may offer relief to patients suffering from chronic neuropathic pain. (Credit: iStockphoto)”
 

“The medicinal use of cannabis has been debated by clinicians, researchers, legislators and the public at large for many years as an alternative to standard pharmaceutical treatments for pain, which may not always be effective and may have unwanted side effects. A new study by McGill University Health Centre (MUHC) and McGill University researchers provides evidence that cannabis may offer relief to patients suffering from chronic neuropathic pain.”

“This is the first trial to be conducted where patients have been allowed to smoke cannabis at home and to monitor their responses, daily,” says Dr. Mark Ware, lead author of the study, who is also Director of Clinical Research at the Alan Edwards Pain Management Unit at the MUHC and an assistant professor of anesthesia in McGill University’s Faculty of Medicine, and neuroscience researcher at the Research Institute of the MUHC.

In this study, low doses (25mg) of inhaled cannabis containing approximately 10% THC (the active ingredient in cannabis), smoked as a single inhalation using a pipe three times daily over a period of five days, offered modest pain reduction in patients suffering from chronic neuropathic pain (pain associated with nerve injury) within the first few days. The results also suggest that cannabis improved moods and helped patients sleep better. The effects were less pronounced in cannabis strains containing less than 10% THC.

“The patients we followed suffered from pain caused by injuries to the nervous system from post-traumatic (e.g. traffic accidents) or post-surgical (e.g. cut nerves) events, and which was not controlled using standard therapies” explains Dr. Ware. “This kind of pain occurs more frequently than many people recognize, and there are few effective treatments available. For these patients, medical cannabis is sometimes seen as their last hope.”

“This study marks an important step forward because it demonstrates the analgesic effects of cannabis at a low dose over a shot period of time for patients suffering from chronic neuropathic pain,” adds Dr. Ware. The study used herbal cannabis from Prairie Plant Systems (under contract to Health Canada to provide cannabis for research and medical purposes), and a 0% THC ‘placebo’ cannabis from the USA.”

Read more:http://www.sciencedaily.com/releases/2010/08/100830094926.htm

Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain: a randomized controlled trial.

“1′,1’dimethylheptyl-Delta8-tetrahydrocannabinol-11-oic acid (CT-3), a potent analog of THC-11-oic acid, produces marked antiallodynic and analgesic effects in animals without evoking the typical effects described in models of cannabinoids. Therefore, CT-3 may be an effective analgesic for poorly controlled resistant neuropathic pain.”

 

“OBJECTIVE: To examine the analgesic efficacy and safety of CT-3 in chronic neuropathic pain in humans.”

 

“CONCLUSIONS: In this preliminary study, CT-3 was effective in reducing chronic neuropathic pain compared with placebo. No major adverse effects were observed.”

 

http://www.ncbi.nlm.nih.gov/pubmed/14519710

Smoked Medicinal Cannabis for Neuropathic Pain in HIV: A Randomized, Crossover Clinical Trial.

“In 1999, a report of the United States Institute of Medicine recommended further investigations of the possible benefits of cannabis (marijuana) as a medicinal agent for a variety of conditions, including neuropathic pain due to HIV distal sensory polyneuropathy (DSPN). The most abundant active ingredient in cannabis, tetrahydro-cannabinol (THC), and its synthetic derivatives, produce effective analgesia in most animal models of pain. The antinociceptive effects of THC are mediated through cannabinoid receptors (CB1, CB2) in the central and peripheral nervous systems, which in turn interact with noradrenergic and κ-opioid systems in the spinal cord to modulate the perception of painful stimuli. The endogenous ligand of CB1, anandamide, itself is an effective antinociceptive agent. In open-label clinical trials and one recent controlled trial, medicinal cannabis has shown preliminary efficacy in relieving neuropathic pain.”

“We conducted a clinical trial to assess the impact of smoked cannabis on neuropathic pain in HIV. This was a phase II, double-blind, placebo-controlled, crossover trial of analgesia with smoked cannabis in HIV-associated distal sensory predominant polyneuropathy (DSPN).”

 “…pain relief was greater with cannabis than placebo…”

 “Smoked cannabis was generally well tolerated and effective when added to concomitant analgesic therapy in patients with medically refractory pain due to HIV DSPN.”

“Our findings suggest that cannabinoid therapy may be an effective option for pain relief in patients with medically intractable pain due to HIV-associated DSPN.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3066045/

Smoked cannabis for chronic neuropathic pain: a randomized controlled trial.

“Cannabis sativa has been used to treat pain since the third millennium BC. An endogenous pain-processing system has been identified, mediated by endogenous cannabinoid ligands acting on specific cannabinoid receptors.These findings, coupled with anecdotal evidence of the analgesic effects of smoked cannabis, support a reconsideration of cannabinoid agents as analgesics.”

“Oral cannabinoids such as tetrahydrocannabinol, cannabidiol and nabilone have, alone and in combination, shown efficacy in central and peripheral neuropathic pain, rheumatoid arthritis and fibromyalgia.”

“We conducted a clinical trial using a standardized single-dose delivery system to explore further the safety and efficacy of smoked cannabis in outpatients with chronic neuropathic pain.”

“Conclusion

A single inhalation of 25 mg of 9.4% tetrahydrocannabinol herbal cannabis three times daily for five days reduced the intensity of pain, improved sleep and was well tolerated.”

“Our results support the claim that smoked cannabis reduces pain, improves mood and helps sleep. We believe that our trial provides a methodological approach that may be considered for further research. Clinical studies using inhaled delivery systems, such as vaporizers, are needed.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2950205/

Low-Dose Vaporized Cannabis Significantly Improves Neuropathic Pain.

“We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment…”

“…cannabis has analgesic efficacy with the low dose being as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well tolerated…”

“Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. PERSPECTIVE: The analgesia obtained from a low dose of delta-9-tetrahydrocannabinol (1.29%) in patients, most of whom were experiencing neuropathic pain despite conventional treatments, is a clinically significant outcome…”

http://www.ncbi.nlm.nih.gov/pubmed/23237736