“Prior phase 2/3 studies found that cannabinoids might provide adjunctive analgesia in advanced cancer patients with uncontrolled pain. To assess adjunctive nabiximols (Sativex®), an extract of Cannabis sativa containing two potentially therapeutic cannabinoids (Δ9-tetrahydrocannabinol and cannabidiol, in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy. Nabiximols was statistically superior to placebo on two of three quality-of-life instruments at week 3 and on all three at week 5. The safety profile of nabiximols was consistent with earlier studies.
Category Archives: Pain
Activation of dorsal horn cannabinoid CB2 receptor suppresses the expression of P2Y12 and P2Y13 receptors in neuropathic pain rats.
“More evidence suggests that dorsal spinal cord microglia is an important site contributing to CB2 receptor-mediated analgesia. The upregulation of P2Y12 and P2Y13 purinoceptors in spinal dorsal horn microglia is involved in the development of pain behavior caused by peripheral nerve injury. However, it is not known whether the expression of P2Y12 and P2Y13 receptors at spinal dorsal horn will be influenced after CB2 receptor activation in neuropathic pain rats. Chronic constriction injury (CCI) and intrathecal ADPbetaS injection were performed in rats to induce neuropathic pain.
In CCI- and ADPbetaS-treated rats, AM1241 pretreatment could efficiently activate CB2 receptor, while inhibiting p38MAPK and NF-kappaB activation in the dorsal spinal cord. CB2 receptor stimulation decreased P2Y13 receptor expression via p38MAPK/NF-kappaB signaling. On the other hand, CB2 receptor activation decreased P2Y12 receptor expression via p38MAPK-independent NF-kappaB signaling pathway.”
https://www.ncbi.nlm.nih.gov/pubmed/28899427
Effects of coadministration of low dose cannabinoid type 2 receptor agonist and morphine on vanilloid receptor 1 expression in a rat model of cancer pain.
“Morphine is widely used as an analgesic to treat moderate to severe pain, but chronic morphine use is associated with development of tolerance and dependence, which limits its analgesic efficacy. Our previous research has showed that nonanalgetic dose of a cannabinoid type 2 (CB2) receptor agonist reduced morphine tolerance in cancer pain. A previous study showed the colocalization of CB2 and transient receptor potential vanilloid 1 (TRPV1) in human and rat dorsal root ganglia (DRG) sensory neurons. Whether coadministration of a CB2 receptor agonist and morphine could reduce TRPV1 expression in morphine‑induced antinociception and tolerance in cancer pain is unclear. Therefore, we investigated the effects of coadministration of a CB2 receptor agonist AM1241 and morphine on TRPV1 expression and tolerance in cancer pain. Coadministration of AM1241 and morphine for 8 days significantly reduced morphine tolerance, as assessed by measuring paw withdrawal latency to a radiant heat stimulation, in Walker 256 tumor‑bearing rats. Repeated morphine treatment for a period of 8 days induced upregulation of the TRPV1 protein expression levels in the DRG in the tumor‑bearing rats, although no change in mRNA expression. Pretreatment with AM1241 reduced this morphine‑induced upregulation of TRPV1 and the effect was reversed by the CB2 receptor antagonist AM630. Our findings suggest that coadministration of a CB2 receptor agonist AM1241 and morphine reduced morphine tolerance possibly through regulation of TRPV1 protein expression in the DRG in cancer pain.”
https://www.ncbi.nlm.nih.gov/pubmed/28901432
https://www.spandidos-publications.com/10.3892/mmr.2017.7479
Tingenone, a pentacyclic triterpene, induces peripheral antinociception due to cannabinoid receptors activation in mice.
“Several works have shown that triterpenes induce peripheral antinociception by activation of cannabinoid receptors and endocannabinoids; besides, several research groups have reported activation of cannabinoid receptors in peripheral antinociception.
The aim of this study was to assess the involvement of the cannabinoid system in the antinociceptive effect induced by tingenone against hyperalgesia evoked by prostaglandin E2 (PGE2) at peripheral level.
The results suggest that tingenone induced a peripheral antinociceptive effect via cannabinoidreceptor activation. Therefore, this study suggests a pharmacological potential for a new analgesic drug.”
https://www.ncbi.nlm.nih.gov/pubmed/28889355
“Cannabis and its psychoactive constituent Δ9-tetrahydrocannabinol (THC) have efficacy against neuropathic pain however, this is hampered by their side-effects. It has been suggested that co-administration with another major constituent cannabidiol (CBD) might enhance the analgesic actions of THC and minimise its deleterious side-effects.
We examined the basis for this phytocannabinoid interaction in a mouse chronic constriction injury (CCI) model of neuropathic pain. Acute systemic administration of THC dose-dependently reduced CCI-induced mechanical and cold allodynia, but also produced motor incoordination, catalepsy and sedation. CBD produced a lesser dose-dependent reduction in allodynia, but did not produce the 
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“Insufficient management of cancer-associated chronic and neuropathic pain adversely affects patient quality of life. Patients who do not respond well to opioid analgesics, or have severe side effects from the use of traditional analgesics are in need of alternative therapeutic op-tions.
Anecdotal evidence suggests that medical cannabis has potential to effectively manage pain in this patient population.
This review presents a selection of representative clinical studies, from small pilot studies conducted in 1975, to double-blind placebo-controlled trials conducted in 2014 that evaluated the efficacy of 
“Patients with endometriosis often suffer from diffuse and poorly localized severe pain. The current pain management strategies include medical and hormonal therapy, as well as surgery. Medical management of pain is often insufficient and is associated with high rate of recurrence. Better pain management is therefore of urgent need.
Methods: Among the various candidates, the endocannabinoid system (ECS) has recently emerged as a relevant pharmacological target for the management of endometriosis-related pain. A computerized literature search was performed to identify relevant studies combining the keywords “endometriosis,” “endocannabinoid,” “
“Cannabis has been used for medical purposes across the world for centuries. As states and countries implement medical and recreational cannabis policies, increasing numbers of people are using cannabis pharmacotherapy for pain. There is a theoretical rationale for cannabis’ efficacy for pain management, although the subjective pain relief from cannabis may not match objective measurements of analgesia. As more patients turn to cannabis for pain relief, there is a need for additional scientific evidence to evaluate this increase.
Discussion: Preclinical studies demonstrate a narrow therapeutic window for cannabis as pharmacotherapy for pain; the body of clinical evidence for this indication is not as extensive. A recent meta-analysis of clinical trials of cannabis and cannabinoids for pain found modest evidence supporting the use of cannabinoid pharmacotherapy for pain. Recent epidemiological studies have provided initial evidence for a possible reduction in opioid pharmacotherapy for pain as a result of increased implementation of medical cannabis regimens.
Conclusion: With increased use of medical cannabis as pharmacotherapy for pain comes a need for comprehensive risk-benefit discussions that take into account cannabis’ significant possible side effects. As cannabis use increases in the context of medical and recreational cannabis policies, additional research to support or refute the current evidence base is essential to attempt to answer the questions that so many healthcare professionals and patients are asking.
Cannabis has been used around the world for centuries and the purpose for its use has varied throughout that time.However, the utilization of cannabis for medicinal purposes has been consistent. Starting with the Chinese around 2900 B.C., many civilizations have transcribed their use of cannabis for a variety of conditions, from joint pain and muscle spasms to conditions such as gout and malaria. While cannabis has been deployed medicinally for myriad medical conditions, the scientific rationale for its efficacy for these conditions is, in many cases, not clear. Four thousand years later, scientists are still trying to determine the exact medical conditions, if any, cannabis is effective in treating.”