The administration of a single dose of whole-plant cannabis via a thermal-metered inhaler is effective and well tolerated among patients suffering from neuropathy (nerve pain), according to clinical trial data published online ahead of print in the Journal of Pain and Palliative Care Pharmacotherapy.
Israeli investigators assessed the efficacy of a novel, portable metered-dose cannabis inhaler in eight subjects diagnosed with chronic neuropathic pain. Researchers reported that the device administered an efficient, consistent, and therapeutically effective dosage of cannabinoids to all participants.
They concluded, “This trial suggests the potential use of the Syqe Inhaler device as a smokeless delivery system of medicinal cannabis, producing a delta-9-THC pharmacokinetic profile with low inter-individual variation of (maximum drug/plasma concentrations), achieving pharmaceutical standards for inhaled drugs.”
A series of clinical trials conducted by investigators affiliated with the Center for Medicinal Cannabis Research at the University of California, San Diego previously determined that the inhalation of whole-plant cannabis is efficacious in the treatment of neuropathic pain.
Full text of the study, “The pharmacokinetics, efficacy, safety, and ease of use of a novel portable metered-dose cannabis inhaler in patients with chronic neuropathic pain: A phase 1a study,” will appear in the Journal of Pain and Palliative Care Pharmacotherapy.
The administration of synthetic cannabinoid agonists limits HIV infection in macrophages (white blood cells that aid in the body’s immune response), according to preclinical data published in the Journal of Leukocyte Biology. Macrophages are one of the first type of cells infected by the HIV virus when it enters the body.
Investigators at Temple University School of Medicine in Philadelphia assessed the impact of three commercially available synthetic THC agonists on HIV-infected macrophage cells. Following administration, researchers sampled the cells periodically to measure the activity of an enzyme called reverse transcriptase (RT), which is essential for HIV replication. By day 7, investigators reported that the administration of all three compounds was associated with a significant decreased in HIV replication.
Stated a Temple University Health System press release: “The results suggest that selective CB2 (cannabinoid 2 receptor) agonists could potentially be used in tandem with existing antiretroviral drugs, opening the door to the generation of new drug therapies for HIV/AIDS. The data also support the idea that the human immune system could be leveraged to fight HIV infection.”
Patients living with HIV/AIDS frequently report consuming cannabis to counter symptoms of anxiety, appetite loss, chronic pain, and nausea, and one study has reported that patients who use cannabis therapeutically are 3.3 times more likely to adhere to their antiretroviral therapy regimens than non-cannabis users. In preclinical models, the long-term administration of delta-9-THC has recently been associated with decreased mortality and ameliorated disease progression in monkeys. In clinical models, cannabis inhalation is associated with decreased neuropathy and increased levels of appetite hormones in the blood of subjects with HIV infection.
The abstract of the study, “Attenuation of HIV-1 replication in macrophages by cannabinoid receptor 2 agonists,” appears online here.
Investigators at the University of California, Davis Medical Center conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in 39 subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Subjects inhaled cannabis of either moderate THC (3.53 percent), low dose THC (1.29 percent), or zero THC (placebo). Subjects continued to take all other concurrent medications as per their normal routine during the 3- to 4-week study period. Spontaneous pain relief, the primary outcome variable, was assessed by asking participants to indicate the intensity of their current pain on a 100-mm visual analog scale (VAS) between 0 (no pain) and 100 (worst possible pain).
Researchers reported: “Both the low and medium doses proved to be salutary analgesics for the heterogeneous collection of neuropathic pain conditions studied. Both active study medications provided statistically significant 30% reductions in pain intensity when compared to placebo.”
They concluded: “Both the 1.29% and 3.53% vaporized THC study medications produced equal antinociception at every time point. … [T]he use of low doses could potentially be prescribed by physicians interested in helping patients use cannabis effectively while minimizing cognitive and psychological side effects. Viewed with this in mind, the present study adds to a growing body of literature supporting the use of cannabis for the treatment of neuropathic pain. It provides additional evidence of the efficacy of vaporized cannabis as well as establishes low-dose cannabis (1.29%) as having a favorable risk-benefit ratio.”
Previous clinical trials have indicated that inhaled cannabis can safety and effectively relieve various types of pain, particularly neuropathy — a hard-to-treat nerve condition often associated with cancer, HIV, spinal cord injury, diabetes, multiple sclerosis, and other conditions. These include the following double-blind, placebo-controlled (FDA gold-standard) studies:
Ware et al. 2010. Smoked cannabis for chronic neuropathic pain: a randomized controlled trial. CMAJ 182: 694-701.
Wilsey et al. 2008. A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. Journal of Pain 9: 506-521.
Ellis et al. 2008. Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology 34: 672-80.
Abrams et al. 2007. Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology 68: 515-521.
Wallace et al. 2007. Dose-dependent Effects of Smoked Cannabis on Capsaicin-induced Pain and Hyperalgesia in Healthy Volunteers Anesthesiology 107: 785-796.
Separate clinical trial data also reports that inhaled “cannabis augments the analgesic effect of opioids” and therefore “may allow for opioid treatment at lower doses with fewer side effects.”
Since 1999, US sales of opiate drugs have tripled in number and in 2010, a record-setting 254 million prescriptions for opioids were filled in the United States — enough to medicate every American adult around the clock for a month. (In particular, the manufacturing of the drug Oxycodone has increased from 8.3 tons in 1997 to 105 tons in 2011, an increase of 1,200 percent.) Overdose deaths from the use of prescription painkillers are also now at record levels, totaling some 15,000 annually — more than triple the total a decade ago.
Full text of the study, “Low-dose vaporized cannabis significantly improves neuropathic pain,” appears in The Journal of Pain.
Scientific Review: “There Is Now Clear Evidence That Cannabinoids Are Useful For The Treatment Of Various Medical Conditions”August 9, 2012
For the second time in recent months, a scientific paper published in a peer-reviewed journal has thoroughly rebutted the present Schedule I status of cannabis under US federal law, which states that the plant and its organic constituents possess a “high potential for abuse,” and that they lack “accepted medical use” and “accepted safety … under medical supervision.”
According to a just published review in the German scientific journal Deutsches Ärzteblatt International, scientific findings from over 100 controlled clinical trials involving either cannabis or its constituents provide “clear evidence that cannabinoids are useful for the treatment of various medical conditions.”
Investigators from the nova-Institute and the Hannover Medical School in Germany reviewed over 100 controlled trials assessing the safety and efficacy of cannabis and cannabinoids.
Researchers reported: “Knowledge about the therapeutic potential of cannabis products has been greatly improved by a large number of clinical trials in recent years. … There is now clear evidence that cannabinoids are useful for the treatment of various medical conditions,” including chronic neuropathy (nerve pain), multiple sclerosis, HIV/AIDS, Gilles de la Tourette syndrome, and other indications.
Regarding the safety profile of cannabis and cannabinoids, investigators determined: “The most common side effects of cannabinoids are tiredness and dizziness (in more than ten percent of patients), psychological effects, and dry mouth. Tolerance to these side effects nearly always develops within a short time. Withdrawal symptoms are hardly ever a problem in the therapeutic setting.”
Authors did express concern that cannabis could pose additional health risks for adolescents and/or pregnant or breast-feeding women, as well as individuals diagnosed with Hepatitis C, severe cardiovascular disease, addictive disorders, or those vulnerable to certain psychiatric disorders, such as schizophrenia.
Investigators acknowledged that cannabis dosing may adversely impact psychomotor skills. However, they noted, “Patients who take cannabinoids at a constant dosage over an extensive period of time often develop tolerance to the impairment of psychomotor performance, so that they can drive vehicles safely.”
They concluded, “No acute deaths have been described that could be unequivocally attributed solely to cannabis consumption or treatment with cannabinoids.”
This most recent paper follows the publication of a similar review, published in May in The Open Neurology Journal. In that paper, investigators with the University of California at San Diego and the University of California, Davis concluded: “Evidence is accumulating that cannabinoids may be useful medicine for certain indications. Based on evidence currently available, the (federal) Schedule I classification (of cannabis) is not tenable; it is not accurate that cannabis has no medical value, or that information on safety is lacking.”
In 2011, the Obama administration — via the United States Drug Enforcement Administration (DEA) — formally denied a nine-year-old administrative petition filed by NORML and a coalition of public interest organizations calling on the agency to initiate hearings to reassess the present classification of marijuana as a schedule I controlled substance. In her denial of the petition, DEA administrator Michele Leonhart alleged: “[T]here are no adequate and well-controlled studies proving (marijuana’s) efficacy; the drug is not accepted by qualified experts. … At this time, the known risks of marijuana use have not been shown to be outweighed by specific benefits in well-controlled clinical trials that scientifically evaluate safety and efficacy.”
Coalition advocates are presently appealing the DEA’s denial of their petition in federal court.
Full text of the most recent study, “The therapeutic potential of cannabinoids,” is available online here.
Over Two-Dozen Controlled Trials Demonstrate Cannabinoids’ “Statistically Significant Pain Relieving Effects”March 7, 2012
[Editor’s note: This post is excerpted from this week’s forthcoming NORML weekly media advisory. To have NORML’s news alerts and legislative advisories delivered straight to your in-box, sign up here.]
Cannabis and its active constituents appear to be safe and modestly effective treatments in patients suffering from a variety of chronic pain conditions, including neuropathy (pain due to nerve damage), according to a literature review to be published in The Clinical Journal of Pain.
An investigator from New York University, Department of Physical Medicine and Rehabilitation, conducted a PubMed search to survey the percentage of positive and negative published randomized controlled trials (RCTs) assessing cannabinoids as treatments for pain. Of the 56 hits generated, 38 published RCTs met inclusion criteria. Of these, “71 percent (27) concluded that cannabinoids had empirically demonstrable and statistically significant pain relieving effects, whereas 29 percent (11) did not.”
Cannabinoids appeared to be most effective in treating hard-to-treat neuropathic pain conditions. “[F]or notoriously difficult to treat conditions such as HIV neuropathy, … cannabinergic pain medicines, particularly inhaled cannabinoid botanicals, are one of the only treatments that have been shown to be safe and effective with the highest levels of evidence,” the review states.
Five to ten percent of the US population is estimated to suffer from neuropathic pain at some point during their lives.
The study concludes, “Overall, based on the existing clinical trials database, cannabinergic pain medicines have been shown to be modestly effective and safe treatments in patients with a variety of chronic pain conditions. … Incorporating cannabinergic medicine topics into pain medicine education seems warranted and continuing clinical research and empiric treatment trials are appropriate.”
A separate paper, published in January in the Harm Reduction Journal, concluded: “Prescribing cannabis in place of opioids for neuropathic pain may reduce the morbidity and mortality rates associated with prescription pain medications and may be an effective harm reduction strategy.”
Full text of the study, “Cannabinergic pain medicine: A concise clinical primer and survey of randomized controlled trial results,” will appear in The Clinical Journal of Pain.