Jump to content
The Corroboree
Sign in to follow this  
LikeAshesWeFade

Just a little theory on noid' addiction.

Recommended Posts

Just throwing it out there, but would CBD not be an effective treatment for cb1 deficiency & or addiction? Considering naltrexone is used for opiate addiction in the same way basically??

post-8096-0-43493400-1411191914_thumb.jp

post-8096-0-02136700-1411191926_thumb.jp

post-8096-0-43493400-1411191914_thumb.jpg

post-8096-0-02136700-1411191926_thumb.jpg

post-8096-0-43493400-1411191914_thumb.jpg

post-8096-0-02136700-1411191926_thumb.jpg

Share this post


Link to post
Share on other sites

Interesting idea. I have no idea if it could work, I don't really understand cannabinoid dependency. An interesting side point here is that naltrexone is not only used for opioid addictions, it is used to treat many different addictive behaviours - alcoholism, bulimia, gambling, self-harm - all respond to naltrexone therapy. The idea is that it blocks the reward mechanism somehow - I don't think they're clear on the details yet, but it appears that these seemingly-diverse behaviours have a common "reward" effect. However trials with cannabinoid-dependent patients on naltrexone have been mixed (in one study, they actually felt more high when on naltrexone!) suggesting that something different is going on there. I realise that's not what you were asking, I just thought it was interesting. One suggestion has been that the endocannabinoid system is also involved in reinforcing addictive behaviours - if this is right, CBD could actually be helpful in a similar way to naltrexone - i.e. not as a specific receptor-antagonist, but for any addiction that is reinforced in that same way (maybe even heroin addiction!, as this study suggests)

Anyway, you may get your answer soon - a UK team is studying this very question right now:

Cannabidiol: a novel treatment for cannabis dependence?
Lead Research Organisation: University College London
Department Name: Clinical Health and Educational Psych

Abstract

In Europe, 1% of all adults and nearly 2% of 14-17 year olds are addicted to cannabis. Rates of cannabis dependence have increased markedly over recent years alongside changes in the ingredients of cannabis available on the market (increasing skunk or sinsemilla with high THC and lacking CBD). Among UK first-time drug treatment clients, cannabis is now the primary addiction in 28% of those entering drug treatment, second only to heroin (41%). At present, clinicians rely on psychological treatments which have very limited effectiveness. There is no pharmacological treatment for cannabis addiction. If we found a safe, effective medicine this could improve treatment in a similar way that various medicines have improved rates of stopping tobacco use. It would also impact on educational/vocational achievement and illegal behaviour, and reduce young people's risks of cannabis-associated mental health problems (e.g. schizophrenia, depression).
Converging preclinical and human research suggests cannabidiol (CBD) to be a highly promising treatment, with excellent tolerability and safety. One of the key consequences of cannabis withdrawal is anxiety and CBD reduces anxiety. CBD has shown promising pro-cognitive and neuroprotective effects which may reverse some of the cognitive deficits associated with cannabis dependence. Our recent research has shown that cannabis dependence is more common in those using 'skunk'. Other data suggest a mechanism by which CBD may be protective against cannabis dependence. A key feature of addiction is that an addict's attention is strongly drawn to cues related to the drug abused over and above other cues and this makes it hard to stop use. Animal evidence suggests that CBD can reduce the ability of drug cues to cause relapse to heroin. In people dependent on cannabis, we have found that CBD reduced attention grabbing by cannabis-related pictures. After CBD, cannabis users rated cannabis pictures as less pleasurable. Thus CBD may reduce the motivating power of drug cues. Overall, evidence now suggests that CBD is a logical treatment for cannabis dependence, by targeting key mechanisms both in dependence and equally importantly, cannabis withdrawal symptoms.
This project's objectives are first to determine the optimal dose of CBD and then to evaluate its efficacy in treating cannabis dependence.
Edited by Anodyne
  • Like 2

Share this post


Link to post
Share on other sites

Hmmm isn't that interesting!! Maybe naltrexone potentiates cannabinoids by working in a similar "neighbourhood" to the opioid receptors. Intriguing!! Thank god somebody is trying it as for me if I've got CBD I literally can bin my bong in a matter of hours! No cravings or nasty withdrawals and the anxiety relief.. OMG

Share this post


Link to post
Share on other sites

A recent review may be of interest:

Are cannabidiol and Δ9 -tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review.

Based on evidence that the therapeutic properties of Cannabis preparations are not solely dependent on the presence of Δ9 -tetrahydrocannabinol (THC), pharmacological studies have been recently carried out with other plant cannabinoids (phytocannabinoids), particularly cannabidiol (CBD) and Δ9 -tetrahydrocannabivarin (THCV). Results from some of these studies have fostered the view that CBD and THCV modulate the effects of THC via direct blockade of cannabinoid type-1 (CB1 ) receptors, thus behaving like first generation CB1 inverse agonists, such as rimonabant. Here we review in vitro and ex vivo mechanistic studies of CBD and THCV, and synthesize data from these studies in a meta-analysis. Synthesized data regarding mechanisms are then used to interpret results from recent preclinical animal studies and clinical trials. The evidence indicates that CBD and THCV are not rimonabant-like in their action, and thus appear very unlikely to produce unwanted central nervous system effects. They exhibit markedly disparate pharmacological profiles particularly at CB1 receptors: CBD is a very low affinity CB1 ligand which can nevertheless affect CB1 activity in vivo in an indirect manner, whilst THCV is a high affinity CB1 ligand and potent antagonist in vitro and yet only occasionally produces effects in vivo resulting from CB1 antagonism. THCV also has high affinity for CB2 and signals as a partial agonist, a departure from both CBD and rimonabant. These cannabinoids illustrate how in vitro mechanistic studies do not always predict in vivo pharmacology, and underlie the necessity of testing compounds in vivo before drawing any conclusion on their functional activity at a given target.

This article deals with some of the pharmacological actions of CBD. Actions at cannabinoid, 5-HT1a and TRPV1 receptors [link] seem to be important for CBD-mediated anxiolytic and anti-addictive activity, as do dopaminergic reward pathways for CB1 agonist-dependent addictions, as Anodyne has covered well [2]

CBD was initially described as possessing little affinity for cannabinoid receptors (Petitet et al., 1998; Thomas et al., 1998). A more recent study, nonetheless, has suggested that CBD can antagonize CB1Rs and CB2Rs at relatively low concentrations (Thomas et al., 2007). This antagonism, however, seems to be non-competitive in nature, with evidence suggesting that CBD could act as a CB1R or CB2R inverse agonist (Pertwee, 2008). Contrasting with these findings, CBD could also facilitate eCB-mediated neurotransmission by decreasing AEA hydrolysis or reuptake (Bisogno et al., 2001).

The findings regarding eCBs involvement in CBD effects, however, have been mainly obtained in studies performed in vitro and little is known about the involvement of these mechanisms in the central effects of the drug. To investigate this issue, we initially tested if facilitation of eCB-mediated neurotransmission could explain the anxiolytic effects of CBD in the dlPAG. This hypothesis was based on our previous study showing that direct injection of AEA into this region induces anxiolytic-like effects that were prevented by prior administration of AM251, a CB1R antagonist (Moreira et al., 2007). Surprisingly, the same dose of AM251 that had antagonized AEA failed to prevent CBD anxiolytic effects in the dlPAG (Campos and Guimarães, 2008). Considering that CBD could also act, at µM concentration range, as an agonist of 5-HT1ARs in vitro (Russo et al., 2005) and in vivo (Mishima et al., 2005), we decided to test if CBD effects would be prevented by local pre-treatment with WAY100635, a selective 5-HT1AR antagonist. Supporting this hypothesis, this drug completely blocked the anxiolytic effects of CBD (Campos and Guimarães, 2008). Following this initial result, we have now confirmed that WAY100635 is able to prevent CBD anxiolytic effects after intracerebral injections into the BNST (Gomes et al., 2011) or dlPAG (Soares et al., 2010) as well as following CBD systemic administration (Resstel et al., 2009). 5-HT1A mechanisms are also responsible for the antidepressive-like effects of CBD in the forced swimming test (Zanelati et al., 2010). Despite these findings, which clearly related 5-HT1A-mediated neurotransmission with CBD anxiolytic and antidepressive effects, more recent results showed that the eCB system is also involved in at least some of the central effects of CBD. For example, the facilitatory effect of intracerebroventricular (i.c.v.) administration of CBD in contextual fear-conditioning extinction was prevented by Rimonabant (Bitencourt et al., 2008). Also, the plastic effects of repeated CBD administration seem to involve eCB mechanisms. For example, chronic CBD treatment was shown to increase adult neurogenesis in the dentate gyrus, an effect that was absent in CB1KO mice (Wolf et al., 2010). In line with these results, the in vitro proliferative effects of CBD on embryonic hippocampal cells were prevented by CB1 or CB2 receptor antagonists (Campos et al., 2010).

We have also recently found that a CB1R antagonist, but not a 5-HT1AR, is able to prevent the effects of CBD in the marble burying test (Casarotto et al., 2010). Although initially proposed as an animal model aimed at detecting possible anxiolytic drug effects, it is now thought to evaluate a natural, repetitive behavior that can become compulsive. This test, therefore, has been proposed to model aspects of obsessive–compulsive disorder (OCD; Thomas et al., 2009). CBD effects in this model, depending on CB1R rather than on 5-HT1AR, gives support to the interpretation that the marble burying test (and OCD) engages brain mechanisms somehow different from those of related to classical animal models of anxiety (Witkin, 2008).

Both CBD and AEA can activate TRPV1Rs (Bisogno et al., 2001). These receptors are expressed in several brain areas related to anxiety such as the amygdala, hippocampus, prefrontal cortex, and PAG (Cristino et al., 2006). Activation of TRPV1 receptors can facilitate glutamate release (Marsch et al., 2007; Xing and Li, 2007), the main excitatory neurotransmitter in the CNS. Since antagonism of glutamate and TRPV1Rs in the dlPAG induce anxiolytic-like effects (Aguiar and Guimarães, 2009; Terzian et al., 2009), we hypothesized that at higher doses CBD could also be activating local TRPV1Rs (directly and maybe by inhibiting AEA metabolism/uptake), facilitating glutamate neurotransmission and increasing anxiety. Corroborating this proposal, we found that a low dose of capsazepine, a TRPV1R antagonist, was able to turn the higher but ineffective dose of CBD into an anxiolytic one (Campos and Guimarães, 2009). Interaction with TRPV1Rs has also been suggested to explain the antipsychotic-like effects of CBD on MK-801 induced disruption of PPI (Long et al., 2006). Other mechanisms have also been proposed to account for the effects of CBD, for example blockade of adenosine uptake (Carrier et al., 2006) and antagonism of the putative cannabinoid receptor GPR55 (Mechoulam et al., 2007). Although the former has been related to CBD anxiolytic properties in a preliminary study (Carrier et al., 2007), the involvement of these mechanisms in the central effects of this drug remains to be further investigated. In summary, preclinical and clinical studies indicate that CBD has therapeutic potential in several neuropsychiatric disorders that depend on multiple mechanisms, including interaction with the eCB system. In addition, considering its safety profile (Mechoulam et al., 2007; Zuardi, 2008; Izzo et al., 2009), CBD could be a useful pharmacological tool to modulate this system.


...the ability of endocannabinoids to modulate mesolimbic DA transmission was uncovered through investigations into the effects of THC. All drugs of abuse increase DA neurotransmission in the NAcc (112, 113) and although some early studies exploring a role for DA in cannabinoid abuse potential yielded incongruent results [e.g., Ref. (114, 115)], today a large body of evidence suggests that marijuana is no exception. Indeed, cannabinoid administration enhances extracellular DA concentrations in the ventral striatum (116119). Further, this effect is dependent on CB1 receptor signaling, as pretreatment with the CB1 receptor antagonist/inverse agonist SR141716A (rimonabant) blocks the ability of THC, or the synthetic cannabinoid receptor agonist WIN 55,212-2 (WIN), to enhance striatal DA levels (119). Seminal single-unit recording data from French et al. (120) show that cannabinoids enhance extracellular DA concentrations in the NAcc through increasing both the baseline firing rates and burst frequency of midbrain DA neurons. These enhancements in VTA DA cell firing are also CB1-dependent as they are attenuated by rimonabant (121).


If you wanted the 'naltrexone of cannabinoids', rimonabant would be another option [see here] There is also a bidirectional regulation of mu-opioid and CB1-cannabinoid receptors - both act to affect dopaminergic reward pathways, reinforcing what Anodyne mentioned.

One idea I'd consider is that a 'dependence' on cannabinoids is complicated by it being an attempt at self-medicating anxiety. Considering CBD has robust anxiolytic activity, cravings for the CBs could be reduced through the effects of reduced anxiety.

TRPV1 shouldn't be neglected: "Emerging evidence indicates that TRPV1 may be related to both the cellular and behavioral effects of addictive drugs." [link] and "[multiple] data suggest a role of brain TRPV1 in mediating drug-seeking behavior, anxiety and depression. However the mechanisms by which TRPV1 modulates such processes are still unclear."

Off topic but anyway: N-acetylcysteine may also be helpful [1, 2]

There are a few pharmacological treatments that could also help.

Edited by Alchemica
  • Like 1

Share this post


Link to post
Share on other sites

I do have some spare NAC in the cupboard too! Definitely will have to get onto capping up some of that aswell! Thanks for the info bro!

Share this post


Link to post
Share on other sites

I have tried several forms of cbd both from hemp and from female flowers in a tincture of ethanol. Personally I found the hemp done nothing but the decarb'd cbd rich ethanol tincture was brilliant for my anxiety.. very fast onset and it relieved some pretty hectic heart rates too!

Share this post


Link to post
Share on other sites

Create an account or sign in to comment

You need to be a member in order to leave a comment

Create an account

Sign up for a new account in our community. It's easy!

Register a new account

Sign in

Already have an account? Sign in here.

Sign In Now
Sign in to follow this  

×