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

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

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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.

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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

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

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“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

Marijuana May Be Effective For Neuropathic Pain.

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“The growing body of evidence that marijuana (cannabis) may be effective as a pain reliever has been expanded with publication of a new study in The Journal of Pain reporting that patients with nerve pain showed reduced pain intensity from smoking marijuana.

Researchers at University of California Davis examined whether marijuana produces analgesia for patients with neuropathic pain. Thirty-eight patients were examined. They were given either high-dose (7%), low-dose (3.5%) or placebo cannabis.

The authors reported that identical levels of analgesia were produced at each cumulative dose level by both concentrations of the agent. As with opioids, cannabis does not rely on a relaxing or tranquilizing effect, but reduces the core component of nociception and the emotional aspect of the pain experience to an equal degree. There were undesirable consequences observed from cannabis smoking, such as feeing high or impaired, but they did not inhibit tolerability or cause anyone to withdraw from the study. In general, side effects and mood changes were inconsequential.

It was noted by the authors that since high and low dose cannabis produced equal analgesic efficacy, a case could be made for testing lower concentrations to determine if the analgesic profile can be maintained while reducing potential cognitive decline.

In addition, the authors said further research could probe whether adding the lowest effective dose of cannabis to another analgesic drug might lead to more effective neuropathic pain treatment for patients who otherwise are treatment-resistant.”

http://www.sciencedaily.com/releases/2008/06/080626150628.htm

Self-medication of a cannabinoid CB2 agonist in an animal model of neuropathic pain.

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“Neuropathic pain is caused by injury to the peripheral or central nervous system (CNS)…”

“…novel approaches for identifying safe and effective analgesics with limited abuse liability are necessary.”

“Cannabinoids share the same target as the psychoactive ingredient in maijuana. Cannabinoids suppress neuropathic nociception through CB1 and CB2 mechanisms. CB1 is predominantly located within the CNS… CB2 activation is not associated with CNS side-effects linked to CB1. However, abuse potential of CB2 agonists is unknown.”

“We used a drug self-administration approach to ask whether rats with a spared nerve injury (SNI) would self-medicate with a CB2 agonist to attenuate a neuropathic pain state…”

 “Our results suggest that cannabinoid CB2 agonists may be exploited to treat neuropathic pain with limited drug abuse liability and central nervous system (CNS) side-effects. These studies validate the use of drug self-administration methods for identifying nonpsychotropic analgesics possessing limited abuse potential…”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3157548/

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

More evidence cannabis can help in neuropathic pain.

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“It’s good to see the trial of smoked cannabis in neuropathic pain reported by Ware and colleagues because smoking is the most common way in which patients try this drug. The authors should be congratulated for tackling the question of whether cannabis helps in neuropathic pain, particularly given that the regulatory hurdles for their trial must have been a nightmare. The question is worth investigating because of the ongoing publicity — which patients see, hear and read — that suggests an analgesic activity of cannabis in neuropathic pain, and because of the paucity of robust evidence for such an analgesic effect. If patients are not achieving a good response with conventional treatment of their pain, then they may, reasonably, wish to try cannabis. If medical cannabis is not available where a patient lives, then obtaining it will take the patient outside of the law, often for the first time in his or her life. Good evidence would at least buttress that decision.”

“This trial adds to the three previous studies of smoked cannabis in neuropathic pain that I could find using PubMed and reference lists…”

“Putting together the four trials of smoked cannabis, the provisional conclusions are that an analgesic effect is evident, that this effect, though not great, may be of use to some patients, and that it often carries with it some adverse effects on the central nervous system (though not obviously so in this trial). These conclusions make biological sense, given that cannabinoids taken orally have shown the same sorts of effects. Interestingly, the “moderate” analgesic effect shown here for neuropathic pain seems to hold true for nociceptive pain.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2950178/

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

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“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.

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“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/