Pharmacology of cannabidiol (CBD)

[queenscarlet88]

Hi all,

Cannabidiol (CBD) is a nonpsychoactive cannabinoid, but it still exerts effects on the brain. I was hoping that somebody might be able to shed some light on what exactly those effects are. Specifically, I am trying to figure out whether CBD is in any way GABAergic.

The Wikipedia article on CBD provides what appears to be a pretty comprehensive overview of the research into CBD's pharmacology:

Cannabidiol has a very low affinity for CB1 and CB2 receptors but acts as an indirect antagonist of their agonists. While one would assume that this would cause cannabidiol to reduce the effects of THC, it may potentiate THC's effects by increasing CB1 receptor density or through another CB1-related mechanism. It is also an inverse agonist of CB2 receptors. Recently, it was found to be an antagonist at the putative new cannabinoid receptor, GPR55, a GPCR expressed in the caudate nucleus and putamen. Cannabidiol has also been shown to act as a 5-HT1A receptor agonist, an action which is involved in its antidepressant, anxiolytic, and neuroprotective] effects. Cannabidiol is an allosteric modulator of μ and δ-opioid receptors. Cannabidiol's pharmacologial effects have also been attributed to PPAR-γ receptor agonism and intracellular calcium release.

GABA isn't mentioned at all here. So why am I worried about it? As I have noted in a couple of other threads, I am a former benzodiazepine addict, so it is imperative that I avoid any GABAergics, especially GABA(A) agonists.

What's giving me pause is that CBD works as an anticonvulsant. According to this article, it enhances the anticonvulsant action of phenobarbitol, which is GABAergic. This worries me.

Interestingly, though, the linked article also says that it "reliably reduced the anticonvulsant potencies of chlordiazepoxide, clonazepam, trimethadione and ethosuximide" (emphasis mine). Chlordiazepoxide and clonazepam are, of course, both benzos. Considering my need to avoid GABAergics, it's a good sign that CBD reduces the activity of chlordiazepoxide and clonazepam, right?

Many thanks to anyone who can help me understand whether there's anything to worry about here.

 

[sekio]

CBD is not directly GABAergic.

Also - consider that not everything that effects GABA is going to have the same effects as benzodiazepines and certainly not their addiction potential - most people find phenobarbital rather... less than fun. (Part of this has to do with pharmacokinetics ... some benzos reach peak brain concentrations very rapidly, but phenobarbital takes quite a while...) Another example: muscimol, the active component of the pseudohallucinogenic Amanita muscaria (fly agaric) - is a GABAa agonist! But when's the last time you saw or heard of a case of Amanita dependency?

If you are worried about dependency, concern yourself instead with the more high-level concept of addiction to euphoriants in general. You may miss the forest for the trees by worrying about neurochemistry, and there are lots of drugs that are plenty addictive yet have nothing at all to do with GABA.

 

[Hammilton]

I've always meant to become dependent on amanitas but I've never had the quantity to do it. Otherwise I'd probably have done so. Especially if I could smoke it or snort it.

 

[Liquid Sunshine]

Why would one want to become dependent on anything

 

[TriputoryHeadicine]

CBD prevents the breakdown of anandamide, which had many incredible benefits, and I believe anti-convulsant is one of those. No time to grab a source, but you'll be able to confirm that. What a lovely molecule : ) Felt like opium in the beggining of my medicinal usuage. no withdrawl symptoms to speak of, after 4 months.

 

[queenscarlet88]

CBD is not directly GABAergic.

Also - consider that not everything that effects GABA is going to have the same effects as benzodiazepines and certainly not their addiction potential - most people find phenobarbital rather... less than fun. (Part of this has to do with pharmacokinetics ... some benzos reach peak brain concentrations very rapidly, but phenobarbital takes quite a while...) Another example: muscimol, the active component of the pseudohallucinogenic Amanita muscaria (fly agaric) - is a GABAa agonist! But when's the last time you saw or heard of a case of Amanita dependency?

If you are worried about dependency, concern yourself instead with the more high-level concept of addiction to euphoriants in general. You may miss the forest for the trees by worrying about neurochemistry, and there are lots of drugs that are plenty addictive yet have nothing at all to do with GABA.

Thank you for responding! I want to clarify that I am not worried about addiction risk per se; rather, I want to avoid ingesting any substance that might rekindle symptoms of benzodiazepine withdrawal. The researcher Heather Ashton has written about the risk of alcohol consumption, for example, to have a "kindling" effect and cause symptoms of benzodiazepine withdrawal to flare up, even after a long period of abstinence.