Cannabinoid Receptors & Anxiety

[Geist89]

The CB1 receptor is a ligand of a good majority of the common cannabinoids. However, I was reading the signaling cascade followed by the stimulation of the metabotropic Gi-protein coupled receptor causes an inhibition of GABA release.

Is this the reason that some people find using cannabis to be anxiogenic?

 

[leungkachong]

Sorry, I don't have lots of time to type right now. I think it's more important to look at the localization of cannabinoid receptors, the amygdala+hippocampus's reciprocal inhibition of alternative kinds of learning, and the nature of entrainment/conditioning of the quick-learned aymgdaloid responses to understand this (as many chronic smokers of chronic start experiencing this every time after one sensitizing experience)

 

[Ham-milton]

I think it has to do with the unusual sorts of thinking that are produced. Unusual thinking patterns = unusual thoughts = scary thoughts = anxiety

 

[shamus]

I'd love to read more on this if anyone can suggest a decent source?

 

[MurphyClox]

No problem, here we go:

"The endocannabinoid system in the processing of anxiety and fear and how CB1 receptors may modulate fear extinction"
Lafenetre, Pauline; Chaouloff, Francis; Marsicano, Giovanni in: Pharmacological Research 2007, 56(5), p.367-381.

Abstract:

A review. The endocannabinoid system recently emerged as an important modulator of many neuronal functions. Among them, the control of anxiety and acquired fear represents nowadays one of the most interesting fields of research. Despite contrasting results obtained by the use of cannabinoid receptor agonists in exptl. animals, there is growing evidence that the physiol. activation of the endocannabinoid system plays a central role in the control of basal anxiety levels and in the modulation of fear responses. This review will summarize recent data on the role of the endocannabinoid system in most commonly used tests of anxiety and in the processing of acquired fear, with particular attention to its involvement in fear extinction. Finally, a neurobiol. model possibly able to implement the role of the endocannabinoid system in these processes will be proposed.

Peace! Murphy

 

[MurphyClox]

Or maybe this (but the 1st one is a review and thought be more comprehensive):

"Effects of cannabinoids on the anxiety-like response in mice"
Rutkowska, Maria; Jamontt, Joanna; Gliniak, Halina in: Pharmacological Reports 2006, 58(2), p.200-206.

Abstract:

Several pieces of anatomical, biochem. and pharmacol. evidence indicate that the endocannabinoid system via CB1 receptors is implicated in the control of emotional behavior. However, previous studies have reported unclear and contradictory results concerning the role of cannabinoids in anxiety. The aim of the present study was to examine the influence of the cannabinoid agonist WIN 55, 212-2 (1 and 5 mg/kg), the CB1 antagonist AM 281 (1, 2 and 4 mg/kg), the inhibitor of anandamide hydrolysis AACOCF3 (1 and 4 mg/kg) and the inhibitor of anandamide transporter AM 404 (1 and 4 mg/kg) on the anxiety-like response in mice in the light/dark box test. WIN 55, 212-2 (5 mg/kg) induced the anxiogenic-like effect accompanied by motor inhibition, AACOCF3 (4 mg/kg) induced the selective anxiolytic-like effect, whereas AM 404 and AM 281 were without effect. Pretreatment with AM 281 (2 mg/kg) blocked the anxiogenic-like and sedative responses induced by WIN 55, 212-2, as well as the anxiolytic-like effect of AACOCF3. These results support the hypothesis that the endocannabinoid system is involved in the regulation of anxiety-like behavior, and also suggest that the inhibitors of anandamide hydrolysis might be potential anxiolytic drugs.

 

[MurphyClox]

Both articles are available for download @Blacklight.

Murphy

 

[suark77]

like cayenne, man

there is a lot of spillover from delta-9...it agonizes the TRPV1 (vallinoid) receptor. heating things up internally, in direct contrast to the neuro-protective actions of that same delta-9, might cause some of that edge.

equally likely (or in conert with) is the metabolite scenario. delta-9 has two active metabolites that last a long time in the body, and while bound to the CBx receptors, they combine with delta-9's own antagonistic effect on the body's own anandamide supply (yes, I mean antagonist effect), there's bound to be a confluence resulting in at least modest anxiety. three chemicals all blocking what the body needs/wants to relax...yuck.

 

[shamus]

equally likely (or in conert with) is the metabolite scenario. delta-9 has two active metabolites that last a long time in the body, and while bound to the CBx receptors, they combine with delta-9's own antagonistic effect on the body's own anandamide supply (yes, I mean antagonist effect), there's bound to be a confluence resulting in at least modest anxiety. three chemicals all blocking what the body needs/wants to relax...yuck.

Hmmmm, so much I don't know

What are the metabolites & how do they 'antagonise' the endogenous anandamide 'supply'?

 

[5-HT2]

^^^Without looking this up, I'm guessing that these metabolites are weak partial agonists or antagonists, or cause desensitization of the receptor, and can therefore act as antagonists of endocannabinoid binding to CB1R. I'm not sure whether the synthesis (e.g. "supply") of anandamide would be affected by CB1 antagonism, but perhaps somebody with more initiative than I can look this up.