Tag Archives: antinociceptive

Antinociceptive activity of Delta9-tetrahydrocannabinol non-ionic microemulsions.

Posted on by
Reply

“Delta(9)-Tetrahydrocannabinol (Delta(9)-THC), the major psychoactive constituent of Cannabis sativa L., has been widely studied for its potential pharmaceutical application in the treatment of various diseases and disturbs.

The aim of this work was to develop a stable aqueous Delta(9)-THC formulation acceptable for different ways of administration, and to evaluate the therapeutic properties of the new Delta(9)-THC based preparation for pain treatment.

Significant antinociceptive activity has been detected by both intraperitoneal and intragastric administration of the new Delta(9)-THC pharmaceutical preparation.”

http://www.ncbi.nlm.nih.gov/pubmed/20399844

CB2 cannabinoid receptor mediation of antinociception.

Posted on by
Reply

“Management of acute pain remains a significant clinical problem. In preclinical studies, CB2 cannabinoid receptor-selective agonists inhibit nociception without producing central nervous system side effects.

The experiments reported here further test the hypothesis that CB2 receptor activation inhibits nociception…

The CB2 receptor-selective agonist produces antinociceptive… activation of CB2 receptors results in antinociception…

…confirm the potential therapeutic relevance of CB2 cannabinoid receptors for the treatment of acute pain.”

http://www.ncbi.nlm.nih.gov/pubmed/16563625

Targeting the cannabinoid system for pain relief?

Posted on by
Reply

“Marijuana has been used to relieve pain for centuries, but its analgesic mechanism has only been understood during the past two decades. It is mainly mediated by its constituents, cannabinoids, through activating central cannabinoid 1 (CB1) receptors, as well as peripheral CB1 and CB2receptors.

CB2-selective agonists have the benefit of lacking CB1 receptor-mediated CNS side effects. Anandamide and 2-arachidonoylglycerol (2-AG) are two intensively studied endogenous lipid ligands of cannabinoid receptors, termed endocannabinoids, which are synthesized on demand and rapidly degraded…

In addition to the antinociceptive properties of  exogenous cannabinoids and endocannabinoids, involving their biosynthesis and degradation processes, we also review recent studies that revealed a novel analgesic mechanism, involving 2-AG in the periaqueductal gray (PAG), a midbrain region for initiating descending pain inhibition…”

http://www.ncbi.nlm.nih.gov/pubmed/24529672

Peripheral interactions between cannabinoid and opioid systems contribute to the antinociceptive effect of crotalphine.

Posted on by
Reply

“Crotalphine is an antinociceptive peptide… we evaluated the involvement of the peripheral cannabinoid system in the crotalphine effect and its interaction with the opioid system…

Crotalphine-induced antinociception involves peripheral CB2 cannabinoid receptors and local release of dynorphin A, which is dependent on CB2 receptor activation.

These results enhance our understanding of the mechanisms involved in the peripheral effect of crotalphine, as well as the interaction between the opioid and cannabinoid systems.”

http://www.ncbi.nlm.nih.gov/pubmed/24460677

Involvement of cannabinoid receptors in peripheral and spinal morphine analgesia.

Posted on by
Reply

“The interactions between the cannabinoid and opioid systems for pain modulation are reciprocal. However, the role and the importance of the cannabinoid system in the antinociceptive effects of opioids remain uncertain. We studied these interactions with the goal of highlighting the involvement of the cannabinoid system in morphine-induced analgesia.

In both phases of the formalin test, intra paw and intrathecal morphine produced similar antinociceptive effects in C57BL/6, cannabinoid type 1 and type 2 receptor wildtype (respectively cnr1WT and cnr2WT) mice. In cnr1 and cnr2 knockout (KO) mice, at the dose used the antinociceptive effect of intra paw morphine in the inflammatory phase of the formalin test was decreased by 87% and 76%, respectively. Similarly, the antinociceptive effect of 0.1 μg spinal morphine in the inflammatory phase was abolished in cnr1KO mice and decreased by 90% in cnr2KO mice. Interestingly, the antinociceptive effect of morphine in the acute phase of the formalin test was only reduced in cnr1KO mice. Notably, systemic morphine administration produced similar analgesia in all genotypes, in both the formalin and the hot water immersion tail flick tests.

Because the pattern of expression of the mu opioid receptor (MOP), its binding properties and its G protein coupling remained unchanged across genotypes, it is unlikely that the loss of morphine analgesia in the cnr1KO and cnr2KO mice is the consequence of MOP malfunction or downregulation due to the absence of its heterodimerization with either the CB1 or the CB2 receptors, at least at the level of the spinal cord.”

http://www.ncbi.nlm.nih.gov/pubmed/24365460

The oral administration of trans-caryophyllene attenuates acute and chronic pain in mice.

Posted on by
Reply

“Trans-caryophyllene is a sesquiterpene present in many medicinal plants’ essential oils, such as Ocimum gratissimum and Cannabis sativa. In this study, we evaluated the antinociceptive activity of trans-caryophyllene in murine models of acute and chronic pain and the involvement of trans-caryophyllene in the opioid and endocannabinoid systems…

 These results demonstrate that trans-caryophyllene reduced both acute and chronic pain in mice, which may be mediated through the opioid and endocannabinoid systems.”

http://www.ncbi.nlm.nih.gov/pubmed/24055516

Differential role of anandamide and 2-arachidonoylglycerol in memory and anxiety-like responses.

Posted on by
Reply

“Cannabinoid agonists are potential therapeutic agents because of their antinociceptive and anxiolytic-like effects…

These results dissociate the role of anandamide and 2-arachidonoylglycerol in memory consolidation and anxiety and reveal the interest of cannabinoid receptor 2 as a novel target for the treatment of anxiety-related disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/21684528

Role of cannabinoids in the management of neuropathic pain.

Posted on by
Reply

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.

Posted on by
Reply

“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/

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/