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This is at the heart of most addiction since dopamine is the workhorse of our reward system. It's even showing in a key part of the brain tied to addiction : We observed a statistically significant increase in striatal dopamine concentrations only with alprazolam, during the period corresponding to the behavioral stimulatory effects. With imaging, researchers were able to see the specific effect in the brain at a specific area: first direct evidence in humans that alprazolam (Xanax) acutely increases perfusion in the nucleus accumbens, a key reward-processing region linked to addiction.

As a whole, the nucleus accumbens has a significant role in the cognitive processing of motivation, aversion, reward (i.e., incentive salience, pleasure, and positive reinforcement), and reinforcement learning. This speaks to this fact: Benzodiazepines’ newly discovered mechanism for producing reward is comparable to those of opiates, cannabinoids, and GHB. This explains why benzos are the follow-up addiction behind opioids. The road to addiction deals with structural changes in the brain as the continued use of benzos starts to change the structure of the brain to respond more strongly to future use: These receptors render the cell more susceptible to stimulation by the excitatory neurotransmitter glutamate, and as a result, the cells respond to future drug exposures with larger dopamine surges that produce even more intense pleasure. their assessment after watching structural changes in the dopamine neurons: Even if you clear the drug from the body, there are long-lasting changes in brain architecture.” Learn more about the sad state of this net effect on addiction at our CBD versus anxiety meds article. Short term cognitive impairment is a known issue but what about longer-term use on the brain? There's a great history and look at damage caused to the brain from longer-term benzo use here: Benzos were never intended to be long term medications and the medical literature speaks to this. Let's look at CBD but first, we need to look at where it operates. We've detailed the endocannabinoid system significantly in our CBD and anxiety article or our CBD and antianxiety medications here.

The endocannabinoid system is critical to balancing other key systems such as : Nervous system - including neurotransmitters like GABA, Serotonin, and others tied to anxiety Endocrine system - hormones including progesterone, estrogen, histamine, and others Immune system - including inflammatory response and cell growth/death cycles. We have naturally occurring cannabinoids that interact with this system. The most prominent in the nervous system (critical to anxiety) are: Since benzo's focus on the GABA levels for anxiety, we'll stay there. It's definitely not the only lever at play with anxiety but we'll leave that to our comprehensive summary of CBD and anxiety above. First, is there any connection between this system and the action of benzos? studies in our laboratory showed that cannabinoid CB1 receptor knockout mice (CB1-/-) presented increased anxiety-like behaviors that did not respond to the anxiolytic actions of benzodiazepines. Let's decipher this a bit because it's really important to our discussion. CB1 is a cannabinoid receptor that's primarily expressed in the brain. This is where cannabinoids like CBD do most of their work. When those receptors were "knocked out" with gene editing in mice, benzos no longer had their anti-anxiety effects! This means that the endocannabinoid system is key not only to the function of benzos in the body but perhaps to the underlying issue with anxiety itself. Taken together, these findings revealed that the cannabinoid CB1 receptor plays a pivotal role in the pharmacological actions of benzodiazepines. Since benzos are just a workaround to increase GABA levels (in terms of anxiety), do endocannabinoids affect GABA directly? Researchers found that cannabinoids do indeed affect not only GABA levels (our nervous system's brake) but also glutamate (our nervous system's gas pedal): Endocannabinoid 2-AG Potentiates GABAA Receptors. This just means that 2-AG boosts the signaling of GABA receptors in the body. Interestingly, the researchers went on to study the effects of 2-AG and a common benzo, diazepam (Valium). They found that 2-AG boosted the effect of diazepam on GABA production : These results clearly suggest a superadditivity between the modulation by diazepam and 2-AG. So, clearly the endocannabinoid system is intimately involved in GABA levels, the means by which benzos have their effects, and anxiety in general). We'll stop there so we can look at CBD directly to see what effect it might have on this pathway. Again, this is not the only pathway we want to explore with anxiety. Check out here: CBD versus benzos for anxiety according to research. We compared CBD and the various classes of anti-anxiety meds including benzos in our comparison page. Let's look specifically at the CBD versus benzos for anxiety. First, does CBD affect the GABA pathway that benzos affect?

There's quite a bit of research now on how CBD boosts GABA signaling and the exact methods of how it does this.

Much of this was found researching its initial effects on epilepsy which is partially an issue of hyper-excitability in parts of the brain (GABA is a brake after all).

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