Tag Archives: tetrahydrocannabinol

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

Posted on by
2

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.

Posted on by
2

“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/

Smoked cannabis proven effective in treating neuropathic pain.

Posted on by
Reply

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

Marijuana Eases Chronic Pain, Researchers Say – ABC News

Posted on by
Reply

“Smoking marijuana modestly reduced pain and other symptoms of chronic neuropathic pain, results of a small trial showed.

The most potent dose used reduced average daily pain scores by 0.7 points on an 11-point scale, according to Mark A. Ware of McGill University in Montreal, Canada and colleagues.

Those who smoked weed with 9.4 percent of the active ingredient tetrahydrocannabinol (THC) also reported sleeping better, the researchers reported online in CMAJ.”

Read more: http://abcnews.go.com/Health/PainManagement/smoking-marijuana-ease-chronic-pain-researchers/story?id=11515566

Marijuana may relieve nerve pain when other drugs don’t – USAToday

Posted on by
Reply
“Smoking cannabis, also known as marijuana, reduced pain in patients with nerve pain stemming from injuries or surgical complications, new research shows.

Twenty-one adults with chronic nerve pain were taught to take a single inhalation of 25 milligrams of cannabis through a pipe, three times a day, for five days. The cannabis contained one of three levels of potency of tetrahydrocannabinol (THC), the active ingredient in marijuana, as well as a placebo dosage containing no THC.

All of the patients rotated through each of the four dosages, with nine days of no smoking in between.

Patients smoking the highest potency marijuana (9.4%) reported less pain than those smoking samples containing no THC. Patients also reported better sleep and less anxiety, according to the Canadian study. 

On an 11-point scale, the average daily pain intensity was 6.1 for those smoking 9.4% THC concentration, compared to 5.4 for those smoking cannabis containing no THC.

“Patients have repeatedly made claims that smoked cannabis helps to treat pain, but the issue for me had always been the lack of clinical research to support that claim,” said Dr. Mark Ware, director of clinical research at the Alan Edwards Pain Management Unit of the McGill University Health Centre in Montreal. In this small but randomized, controlled trial, “the pain reductions were modest, but significant,” he said. “And it was in people for whom nothing else worked.”

Read more: http://usatoday30.usatoday.com/yourlife/health/medical/2010-09-05-marijuana-pain_N.htm

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

Posted on by
Reply

“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.

Posted on by
Reply

“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.

Posted on by
Reply

“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

Cannabis eases multiple sclerosis (MS) stiffness: study

Posted on by
Reply

“Use of cannabis extract helps ease painful muscle stiffness among patients with multiple sclerosis (MS), according to a large trial published on Tuesday in the Journal of Neurology, Neurosurgery and Psychiatry.

The “Phase III” test — the final stage in a process to vet a new drug or medical process — took place among 22 centres in Britain.

Over 12 weeks, 144 patients were given daily tablets of tetrahydrocannabinol, which is the active ingredient in cannabis, and 135 were given a dummy pill, also called a placebo…

…They also reported improvement in sleep quality. Side effects were nervous system disorders and gut problems, but none was severe…

The trial, led by John Peter Zajicek of Britain’s Clinical Neurology Research Group, says standardized doses of cannabis extract can be useful in easing pain and spasms in this disease.

Previous Phase III trials on cannabis and MS have thrown up conflicting results, partly because of the scale by which users report any change in their symptoms, the MUSEC researchers said.”

http://articles.nydailynews.com/2012-10-10/news/34367509_1_multiple-sclerosis-cannabis-nerve-cells

A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms.

Posted on by
Reply

“OBJECTIVES:

To determine whether plant-derived cannabis medicinal extracts (CME) can alleviate neurogenic symptoms unresponsive to standard treatment, and to quantify adverse effects.

SUBJECTS:

Twenty-four patients with multiple sclerosis (18), spinal cord injury (4), brachial plexus damage (1), and limb amputation due to neurofibromatosis (1).

INTERVENTION:

Whole-plant extracts of delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), 1:1 CBD:THC, or matched placebo were self-administered by sublingual spray at doses determined by titration against symptom relief or unwanted effects within the range of 2.5-120 mg/24 hours. Measures used: Patients recorded symptom, well-being and intoxication scores on a daily basis using visual analogue scales. At the end of each two-week period an observer rated severity and frequency of symptoms on numerical rating scales, administered standard measures of disability (Barthel Index), mood and cognition, and recorded adverse events.

RESULTS:

Pain relief associated with both THC and CBD was significantly superior to placebo. Impaired bladder control, muscle spasms and spasticity were improved by CME in some patients with these symptoms. Three patients had transient hypotension and intoxication with rapid initial dosing of THC-containing CME.

CONCLUSIONS:

Cannabis medicinal extracts can improve neurogenic symptoms unresponsive to standard treatments. Unwanted effects are predictable and generally well tolerated. Larger scale studies are warranted to confirm these findings.”

http://www.ncbi.nlm.nih.gov/pubmed/12617376