“The quest for possible targets for the development of novel analgesics has identified the activation of the cannabinoid type 1 (CB1) receptor outside the CNS as a potential means of providing relief from persistent pain, which currently constitutes an unmet medical need.
Increasing tissue levels of the CB1 receptor endogenous ligand N-arachidonoylethanolamine (anandamide), by inhibiting anandamide degradation through blocking the anandamide-hydrolysing enzyme fatty acid amide hydrolase, has been suggested to be used to activate the CB1 receptor.
However, recent clinical trials revealed that this approach does not deliver the expected relief from pain. Here, we discuss one of the possible reasons, the activation of the transient receptor potential vanilloid type 1 ion channel (TRPV1) on nociceptive primary sensory neurons (PSNs) by anandamide, which may compromise the beneficial effects of increased tissue levels of anandamide.
We conclude that better design such as concomitant blocking of anandamide hydrolysis and anandamide uptake into PSNs, to inhibit TRPV1 activation, could overcome these problems.”
“Although originally described as a signalling system encompassing the cannabinoid CB1 and CB2 receptors, their endogenous agonists (the endocannabinoids), and metabolic enzymes regulating the levels of such agonists, the endocannabinoid system is now viewed as being more complex, and including metabolically related endocannabinoid-like mediators and their molecular targets as well.
The function and dysfunction of this complex signalling system in the molecular and cellular mechanisms of pain transduction and control has been widely studied over the last two decades.
In this review article, we describe some of the latest advances in our knowledge on the role of the endocannabinoid system, in its most recent and wider conception, in pain pathways, by focusing on: (1) neuron-glia interactions; and (2) emerging data on endocannabinoid cross-talk with neurotrophins, such as nerve growth factor and brain-derived neurotrophic factor.”
“Although pain is multifactorial at cellular and molecular levels, it is widely accepted that neurotrophin (TrkA, p75NTR, Ret and GFRs), cannabinoid (CB1 and CB2), and thermo-transient receptor potential (TRPs; TRPV1, TRPA1 and TRPM8) receptors play a pivotal role.
…the available information confirms that pharmacological modulation of this signalling triad is a highly valuable therapeutic strategy for effectively treating pain syndromes.”
“Cannabis has been used for centuries for both symptomatic and prophylactic treatment of different types of headaches including migraine…
Suppression of CSD (cortical spreading depression) by activation of CB1 receptors suggests the potential therapeutic effects of cannabinoids in migraine with aura as well as other CSD-related disorders.”
“The use of cannabis for medical purposes is proliferating in the U.S., and PTSD is an explicitly approved condition for accessing medical cannabis in 5 states. Prior research suggests that people with PTSD often use cannabis to help cope with their condition…
Those with high PTSD scores were more likely to use cannabis to improve sleep, and for coping reasons more generally, compared with those with low PTSD scores. Cannabis use frequency was greater among those with high PTSD scores who used for sleep promoting purposes compared with those with low PTSD scores or those who did not use for sleep promoting purposes.
Consistent with prior research, this study found increased rates of coping-oriented use of cannabis and greater frequency of cannabis use among medical users with high PTSD scores compared with low PTSD scores. In addition, sleep improvement appears to be a primary motivator for coping-oriented use…”
“In the present study, the effects of bilateral microinjections of cannabinoid CB1 receptor agonist and antagonist into the basolateral amygdala (intra-BLA) on nicotine-induced place preference were examined in rats.
Taken together, these findings support the possible role of endogenous cannabinoid system of the BLA in the acquisition and the expression of nicotine-induced place preference. Furthermore, it seems that there is a functional interaction between the BLA cannabinoid receptors and nicotine in producing the rewarding effects.”
“Stress-exposure produces excitoxicity and neuroinflammation, contributing to the cellular damage observed in stress-related neuropathologies. The endocannabinoid system is present in stress-responsive neural circuits and it is emerging as a homeostatic system. The aim of this study was to elucidate the possible regulatory role of cannabinoid-2 receptor in stress-induced excitotoxicity and neuroinflammation.
CONCLUSIONS AND IMPLICATIONS:
These results suggest that pharmacological manipulation of CB2 receptor is a potential therapeutic strategy for the treatment of stress-related pathologies with a neuroinflammatory component, such as depression.”
“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.”