“Preclinical studies demonstrate that cannabinoid-mediated antinociceptive effects vary according to sex; it is unknown if these findings extend to humans.
These results indicate that in cannabis smokers, men exhibit greater cannabis-induced analgesia relative to women.
As such, sex-dependent differences in cannabis’s analgesic effects are an important consideration that warrants further investigation when considering the potential therapeutic effects of cannabinoids for pain relief.”
“Cannabis species have been used as medicine for thousands of years; only since the 1940s has the plant not been widely available for medical use.
However, an increasing number of jurisdictions are making it possible for patients to obtain the botanical for medicinal use.
For the cancer patient, cannabis has a number of potential benefits, especially in the management of symptoms. Cannabis is useful in combatting anorexia, chemotherapy-induced nausea and vomiting, pain, insomnia, and depression.
Cannabis might be less potent than other available antiemetics, but for some patients, it is the only agent that works, and it is the only antiemetic that also increases appetite.
Inhaled cannabis is more effective than placebo in ameliorating peripheral neuropathy in a number of conditions, and it could prove useful in chemotherapy-induced neuropathy.
A pharmacokinetic interaction study of vaporized cannabis in patients with chronic pain on stable doses of sustained-release opioids demonstrated no clinically significant change in plasma opiates, while suggesting the possibility of synergistic analgesia.
Aside from symptom management, an increasing body of in vitro and animal-model studies supports a possible direct anticancer effect of cannabinoids by way of a number of different mechanisms involving apoptosis, angiogenesis, and inhibition of metastasis.
Despite an absence of clinical trials, abundant anecdotal reports that describe patients having remarkable responses to cannabis as an anticancer agent, especially when taken as a high-potency orally ingested concentrate, are circulating.
Human studies should be conducted to address critical questions related to the foregoing effects.”
“The objective of this study was to explore the potential role of G-protein-coupled receptor kinase 2 (GRK2) in the progression of cannabinoid 2 receptor (CB2) agonist-induced analgesic effects of bone cancer pain.
The results affirmed CB2 receptor agonists might serve as new treatment targets for bone cancer pain.
Moreover, spinal GRK2 was an important regulator of CB2 receptor agonist-analgesia pathway.”
“Cannabinoids produce analgesia through a variety of mechanisms.
It has been proposed that one mechanism is by modulating the release of CGRP in the spinal cord pain pathways.
Previous studies have reported that cannabinoids, particularly CB2 receptor agonists, can modulate CGRP release in the isolated rat spinal cord.
These results question the role of spinal cord cannabinoid receptors in the regulation of CGRP signalling.”
“Cannabinoids produce analgesia in several pain models, but the undesirable side effects from high doses of cannabinoid drugs limit their clinic use.
Our recent results indicate that cannabinoid-induced antinociception was enhanced by neuropeptide VF (NPVF).
Here, we investigate whether low-dose cannabinoid agonists combined with NPVF can produce effective antinociception with limited side effects…
These data suggest that the cannabinoid agonist combined with NPVF produces effective antinociception-lacking tolerance via both cannabinoid receptor type 1 and neuropeptide FF receptors in the brain.”
“Diabetic neuropathic pain is one of the most commonly encountered neuropathic pain syndromes.
It is well known that diabetic animals are less sensitive to the analgesic effect of morphine, and opioids are found to be ineffective in the treatment of diabetic neuropathic pain.
Cannabinoids are promising drugs and they share a similar pharmacological properties with opioids.
It has been reported that cannabinoid analgesia remained intact and to be effective in some models of nerve injury.
Thus, we investigated antinociceptive efficacy and the effects of cannabinoids on behavioral sign of diabetic neuropathic pain in diabetic mice by using WIN 55, 212-2, a cannabinoid receptor agonist.
This study suggests that cannabinoids have a potential beneficial effect on experimental diabetic neuropathic pain.”
“While recreational marijuana users may seek the full range of its effects, broad medical use of THC—including for pain, nausea, and anxiety—is hindered by them.
In a new study, Xavier Viñals, Estefania Moreno, Peter McCormick, Rafael Maldonado, Patricia Robledo, and colleagues demonstrate that the cognitive effects of THC are triggered by a pathway separate from some of its other effects.
That pathway involves both a cannabinoid receptor and a serotonin receptor, and when this pathway is blocked, THC can still exert several beneficial effects, including analgesia, while avoiding impairment of memory.
The results of this study are potentially highly important, in that they identify a way to reduce some of what are usually thought of as THC’s unwanted side effects when used for medicinal purposes while maintaining several important benefits, including pain relief.
The widening acceptance of a role for THC in medicine may be accelerated by the option to reduce those side effects by selective pharmacological disruption or blocking of the heteromer.”
http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1002193
“Although cannabinoids have been recreationally employed for thousands of years, it was not until the discovery of their specific receptors, in the early nineties, that the molecular basis of cannabinoid activity have began to be understood.
Growing research in this field has demonstrated not only that the action of cannabinoids in mammals is mainly receptor-mediated, but also that endogenous cannabinoids, such as anandamide, are produced, metabolized, and taken up across the cell membrane through a facilitated uptake process.
The exogenous administration of cannabinoids, as well as the manipulation of their endogenous levels have been related to a variety of effects, such as analgesia, (temporary) impairment of cognition and learning, appetite enhancement and peripheral vasodilation.
Hence, the endocannabinoid system, including the CB1 and CB2 receptors, the metabolizing enzyme fatty acid amide hydrolase and the anandamide transporter, is a potential target for the development of novel therapeutic drugs in the treatment of various conditions, such as pain, feeding disorders and vascular disease among others.
Although most of the research in the field of cannabinoids has been focused on their effects in the central nervous system, a growing line of evidence indicates that cannabinoids can also play a major role in the control of physiopathological functions in the cardiovascular system.
In this context, endocannabinoids have been proposed as novel possible hypotensive agents, and have been involved in the hypotension observed in septic shock, acute myocardial infarction and cirrhosis. In addition, a protective role for endocannabinoids has been described in ischemia.”
“The opioid and non-opioid types of stress-induced analgesia have been well defined. One of the non-opioid type involve the endocannabinoid system.
We previously reported that the spinal serotonin 7 receptor (5-HT7) blockers inhibit both morphine and cannabinoid-induced analgesia, thus we hypothesized that descending serotonergic pathways-spinal 5-HT7 receptor loop might contribute to stress-induced analgesia…
These results indicate that descending serotonergic pathways and the spinal 5-HT7 receptor loop play a crucial role in mediating both opioid and non-opioid type stress-induced analgesia.”
“The Cannabis sativa plant has been exploited for medicinal, agricultural and spiritual purposes in diverse cultures over thousands of years.
Cannabis has been used recreationally for its psychotropic properties, while effects such as stimulation of appetite, analgesia and anti-emesis have lead to the medicinal application of cannabis.
Indeed, reports of medicinal efficacy of cannabis can been traced back as far as 2700 BC, and even at that time reports also suggested a neuroprotective effect of the cultivar.
…alterations in the endocannabinoid system have been extensively investigated in a range of neurodegenerative disorders.
In this review we examine the evidence implicating the endocannabinoid system in the cause, symptomatology or treatment of neurodegenerative disease. We examine data from human patients and compare and contrast this with evidence from animal models of these diseases. On the basis of this evidence we discuss the likely efficacy of endocannabinoid-based therapies in each disease context.
There has been anecdotal and preliminary scientific evidence of cannabis affording symptomatic relief in diverse neurodegenerative disorders. These include multiple sclerosis, Huntington’s, Parkinson’s and Alzheimer’s diseases, and amyotrophic lateral sclerosis.
This evidence implied that hypofunction or dysregulation of the endocannabinoid system may be responsible for some of the symptomatology of these diseases.”