“Since the cannabinoid CB1 receptor modulates various types of aversive responses, this study tested the hypothesis that enhancement of endocannabinoid signalling in the dorsolateral periaqueductal grey inhibits panic-like reactions in rats…
The present results confirm the anti-aversive property of direct CB1 receptor activation in the dorsolateral periaqueductal grey…
Altogether, these results suggest that anandamide signalling is recruited only under certain types of aversive stimuli.”
“Endocannabinoids (ECBs) such as anandamide (AEA) act by activating cannabinoid type 1 (CB1) or 2 (CB2) receptors. The anxiolytic effect of drugs that facilitate ECB effects is associated with increase in AEA levels in several encephalic areas, including the prefrontal cortex (PFC).
Activation of CB1 receptors by CB1 agonists injected directly into these areas is usually anxiolytic.
However, depending on the encephalic region being investigated and on the stressful experiences, opposite effects were observed, as reported in the ventral HIP. In addition, contradictory results have been reported after CB1 activation in the dorsal HIP (dHIP).
Therefore, in the present paper we have attempted to verify if directly interfering with ECB metabolism/reuptake in the prelimbic (PL) portion of the medial PFC (MPFC) and dHIP would produce different effects in two conceptually distinct animal models: the elevated plus maze (EPM) and the Vogel conflict test (VCT).
We observed drugs which interfere with ECB reuptake/metabolism in both the PL and in the dentate gyrus of the dHIP induced anxiolytic-like effect, in both the EPM and in the VCT via CB1 receptors, suggesting CB1 signaling in these brain regions modulate defensive responses to both innate and learned threatening stimuli.
This data further strengthens previous results indicating modulation of hippocampal and MPFC activity via CB1 by ECBs, which could be therapeutically targeted to treat anxiety disorders.”
“Disturbances in the regulation of reward and aversion in the brain may underlie disorders such as obesity and eating disorders.
We previously showed that the cannabis receptor (CB1) inverse agonist rimonabant, an anti-obesity drug withdrawn due to depressogenic side effects, diminished neural reward responses yet increased aversive responses. Unlike rimonabant, tetrahydrocannabivarin (THCv) is a neutral CB1 receptor antagonist and may therefore produce different modulations of the neural reward system…
Conclusions: Our findings are the first to show that treatment with the CB1 neutral antagonist THCv increases neural responding to rewarding and aversive stimuli.
This effect profile suggests therapeutic activity in obesity, perhaps with a lowered risk of depressive side effects.”
“Direct activation of the cannabinoid CB1 receptor in the dorsolateral periaqueductal gray (dlPAG) inhibits anxiety- and panic-related behaviours in experimental animals. It has remained unclear, however, whether the local endocannabinoid signalling is recruited as a protective mechanism against aversive stimuli.
The present study tested the hypothesis that the endocannabinoid system counteracts aversive responses in the dlPAG-stimulation model of panic attacks…
The endocannabinoid system in the dlPAG attenuates the behavioural, cellular and cardiovascular consequences of aversive stimuli. This process may be considered for the development of additional treatments against panic and other anxiety-related disorders.”
“The use of cannabis for medicinal purposes is becoming more prevalent.
For this purpose, various preparations of cannabis of varying strengths and content are being used.
The recent changes in the legal environment have improved the availability of products with high cannabidiol (CBD) and low tetrahydrocannabinol (THC) concentrations.
There is some anecdotal evidence of their potential efficacy, but the mechanisms of such action are not entirely clear.
Some suspect an existence of synergy or “entourage effect” between CBD and THC.
There is strong evidence that THC acts via the cannabinoid receptor CB1.
The mechanism of action of CBD is less clear but is likely polypharmacological.
The scientific data support the role of the endocannabinoid system in seizure generation, maintenance, and control in animal models of epilepsy.
There are clear data for the negative effects of cannabis on the developing and mature brain though these effects appear to be relatively mild in most cases.
Further data from well-designed studies are needed regarding short- and long-term efficacy and side effects of CBD or high-CBD/low-THC products for the treatment of seizures and epilepsy in children and adults.”
“Burn injury causes nociceptive behaviors, and inflammation-related pathologic pain can lead to glial cell activation. This study tested the hypothesis that burn injury activates glial cells, and cannabinoid receptor 1 (CB1R) antagonist, AM251, will decrease burn pain.
AM251 inhibited nociceptive behaviors after burn even beyond 7-day period of administration. Although many studies have documented the utility of CB1R agonists, this study indicates that endogenous cannabinoids may have an unexpected pronociceptive effect during development of burn pain, explaining why CB1R antagonist, AM251, improves nociceptive behaviors.”
“Smoking marijuana doesn’t have to be a bad thing – Especially if you have HD.
The idea that THC can be used to relieve disease symptoms isn’t a new thing – Glaucoma, HIV, and cancer patients have all benefited from the use of CB1 agonists whether in the form of marijuana leaves or a pharmacologically similar product (like dronabinol).
Nevertheless, the idea of using THC or other CB1 agonists for the treatment of HD is pretty new…
The results of this study suggest that THC and other CB1 compounds may not only be able to improve symptoms in already symptomatic HD patients, but also slow down the progression of such a devestating disease.
Good news all around and a great use of THC as far as I’m concerned (medical use and removal from schedule-1 anyone?!).”
“Direct acting antivirals have significantly improved treatment outcomes in chronic hepatitis C (CHC), but side effects, drug resistance and cost mean that better treatments are still needed.
Lipid metabolism is closely linked with hepatitis C virus (HCV) replication and endocannabinoids are major regulators of lipid homeostasis.
The cannabinoid 1 (CB1) receptor mediates these effects in the liver.
Here we investigated whether CB1 blockade inhibits HCV replication.
The antiviral effect of a CB1 antagonist, AM251 was examined…
Treatment with AM251 strongly inhibited HCV RNA (~70%), viral protein (~80%), the production of new virus particles (~70%), and virus infectivity (~90%)…
We suggest that CB1 antagonists may represent an entirely new class of drugs with activity against HCV.
“Endocannabinoids act as retrograde messengers that, by inhibiting neurotransmitter release via presynaptic CB(1) cannabinoid receptors, regulate the functionality of many synapses. In addition, the endocannabinoid system participates in the control of neuron survival.
Thus, CB(1) receptor activation has been shown to protect neurons from acute brain injury as well as in neuroinflammatory conditions and neurodegenerative diseases.
Cannabinoid neuroprotective activity relies on the inhibition of glutamatergic neurotransmission and on other various mechanisms, and is supported by the observation that the brain overproduces endocannabinoids upon damage.
Besides promoting neuroprotection, a role for the endocannabinoid system in the control of neurogenesis from neural progenitors has been put forward. In addition, activation of CB(2) cannabinoid receptors on glial cells may also participate in neuroprotection by limiting the extent of neuroinflammation.
Altogether, these findings support that endocannabinoids constitute a new family of lipid mediators that act as instructive signals in the control of neuron survival.”
“The centrally expressed cannabinoid receptor (CB1) has been considered a potential therapeutic target in treating alcoholism.
Though CB1 receptors have been shown to modulate primary and conditioned ethanol reward, much of this research employed animal models that require ethanol ingestion or oral routes of administration. This is problematic considering CB1 antagonist drugs have high anorectic liability and have been used clinically in the treatment of obesity. Therefore, the present study examined CB1 antagonism in DBA/2J mice using an unbiased ethanol-induced conditioned place preference (CPP) procedure, a paradigm that does not require ethanol ingestion…
Results from the present study appear inconsistent with other studies that have demonstrated a role for CB1 antagonism in ethanol reward using oral administration paradigms.
Our findings suggest that CB1 antagonism may have greater involvement in consummatory behavior than ethanol reward.”