5 New Anxiety Treatments in Development

An interesting article looking at possible new anxiety treatments. The reason I am sharing this is not to condone any new treatment or old treatment but to highlight that in 2015 there are people still looking to address this debilitating illness.

5 New Anxiety Medications In Development (2015)

There are currently many different types of medications that can be utilized to treat anxiety (list of anxiolytics). The problem is that many of the drugs are poorly tolerated and/or produce significant unwanted side effects. Perhaps the most effective class of drugs to treat anxiety are the benzodiazepines as they provide rapid and significant relief.

The problem with the benzos is that they impair cognitive function while taking them, and long-term usage could lead to permanent memory impairment. (Read: Dementia linked to benzodiazepines). Ultimately most people end up better off (in terms of health) pursuing natural cures for anxiety such as taking up a meditation practice, partaking in cognitive behavioral therapy (CBT), reducing stress, and getting more exercise.

That said, there are people that have explored every logical method of biohacking their mental health and have still not been able to find relief. Sometimes people may genuinely need a medication to help them cope with their reality. Fortunately there are always new drugs on the horizon that give people who are struggling hope that one will be a “magic bullet.”

New Anxiety Medications In Development (2015)

In the United States, there are approximately 40 million people with anxiety disorders. Many of these individuals feel as if their anxiety is so bad, they can’t work, talk, sleep, eat or function. If you happen to be struggling with significant anxiety, you may feel hopeful that there are new anxiolytics on the horizon that may be more effective and safer than older options.

1. Aloradine (PH94B)

This is a drug that has been in Phase III clinical trials since 2013 for the treatment of social anxiety disorder in women. It is being developed by the company Pherin Pharmaceuticals in the format of a “nasal spray.” Of all the treatments for anxiety disorders in the pipeline, this one appears to have the most promise of actually making it to market.

What’s unique about Aloradine is that it is a new class of treatments called “pherines.” Pherines are compounds that directly influence targeted areas of the brain without circulating through the bloodstream to produce an effect. Aloradine is administered via nasal spray and is able to directly target peripheral receptors from “nasal chemosensory neurons” that are linked to the hypothalamus/limbic system of the brain. Its particular mechanism of action results in rapid relief from anxiety, and thus far it has been found to be both safe and very tolerable.

This “nasal spray” format may be favorable to antidepressant medications due to the fact that they often take weeks before a person experiences an anxiolytic effect.  Even beta blockers for anxiety can take between 30 and 60 minutes before a person notices their full effect. With Aloradine, one spray can provide seemingly immediate relief. That said, I’m still not sure why the product is tailored specifically for women with anxiety.

The company developing this substance is known as Pherin Pharmaceuticals and focuses specifically on working with “pherins” to alter neuropsychiatric and neuroendocrine function within humans. They have other molecules in development for the treatment of depression, premenstrual dysphoria, and cognitive enhancement.
  • Source: http://www.pherin.com/products.html
  • Source: http://ajp.psychiatryonline.org/doi/abs/10.1176/appi.ajp.2014.12101342

2. B-GOS

This is a prebiotic, or non-digestible food ingredients that improve healthy by stimulating the production of beneficial bacteria in the colon. It has long been thought that a person’s gut flora (or bacteria) may play a role in determining whether they develop a mental illness or experience anxiety. Additionally, there is evidence demonstrating that most pharmaceutical drugs (e.g. antidepressants) have detrimental effects upon a person’s gut flora.

Clasado Biosciences Limited currently are testing “B-GOS” in Phase I clinical trials. B-GOS is considered a unique “trans-galactooligosaccharide” and thus far has been shown to be effective in the reduction of anxiety. In preliminary research, it has been found to decrease both “waking cortisol levels” as well as “attentional vigilance towards negative information.”

People who are overstimulated tend to have high levels of cortisol production, and often get caught up in negative thinking. It seems as though this prebiotic substance may provide some degree of relief. Early evidence also suggests that the substance may alter the functioning of the HPA (hypothalamic-pituitary-adrenal) axis. Individuals suffering from anxiety often have varying degrees of dysfunction within the HPA axis.

Some speculate that this substance may also prove to have therapeutic effects among individuals suffering from depression. There is mounting evidence that gut bacteria may be directly influencing brain function. Altering the gut microbiome may drastically change your mental health and/or cognition.

3. IW-2143 (BNC210)

This is an experimental anxiolytic medication undergoing clinical trials, but there’s currently no information regarding its mechanism of action. It has demonstrated a potent anxiolytic effect in animal subjects as well as in Phase I clinical trials. The good news is that it is unlikely to impair cognitive function, it isn’t addictive (in rodent models), and won’t make you feel sedated. No major side effects have been reported during the early stages of trials.

This drug is a “small molecule” that was discovered by the company Bionomics through a medicinal-chemistry program. Some evidence has shown that the molecule is capable of promoting “neurite” outgrowth (e.g. axon/dendrite). The company developing this drug (Bionomics) is a biotech company that is focused on creating therapies for CNS disorders. They have since licensed “BNC210″ to Ironwood Pharmaceuticals, who refer to it as “IW-2143.”

4. S32212

This is a substance that is under investigation as a potential antidepressant with anxiolytic properties. It functions as a selective, inverse agonist at the 5-HT2C receptor, and Alpha-2 adrenergic receptor antagonist. It also elicits an effect upon the 5-HT2A receptor and a minimal one on the 5-HT2B receptor as an antagonist.

The good news is that it is thought to not affect histamine or acetylcholine receptors. Many drugs that affect H1 histamine and mACh receptors tend to result in memory impairment. Should this drug ever make it to the market, it will likely be classified as an NaSSA (noradrenergic and specific serotonergic antidepressant); the same classification of Remeron.

Based on animal research, this drug elevated levels of BDNF with the amygdala and hippocampus of the brain. It also amplified the amount of neuronal firing within other locations, while increasing neurotransmitters like norepinephrine, dopamine, and acetylcholine (in the prefrontal cortex). It didn’t affect serotonin or histamine (which is probably a good thing).

Researchers have noted a variety of effects resulting from this substance including: antidepressant, anxiolytic, anti-obsessional, as well as anti-aggressive behaviors. It also is thought to enhance sleep and cognition in animals without any signs of weight fluctuation or diminished sex drive. Some speculate that it may even result in weight loss due to its “alpha blocking” effect.
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/22178753

5. SL-651,498

This is a drug that has long been used as an anxiolytic in scientific research, but wasn’t considered for human usage until 2006. In 2008, a report surfaced that preliminary human trials were underway and that the drug was considered as effective as Ativan in reducing anxiety, yet produced minimal sedation, cognitive impairment, or reduction in motor skills. This provides some early evidence that SL-651,498 may be an effective treatment.

Although its anxiolytic potential is equal to that of benzodiazepines, it is structurally distinct from the benzo classification. It has been classified as a “nonbenzodiazepine anxiolytic.” It functions as a subtype-selective GABAA agonist, and elicits primarily anxiolytic effects in animals (with minor sedation). Early research has also suggested that the drug is unlikely to produce dependence or tolerance due to its low affinity for the Alpha-5 receptor.

From the little research there is, it appears as though this substance has some advantages over benzodiazepines. I’m not sure if we should buy into the lack of sedation and no cognitive impairment quite yet. Even if the cognitive impairment isn’t “significant” in preliminary research, I wouldn’t be surprised if it hampered cognition in later trials. In the coming years, we should get a better understanding of SL-651,498.

Which of these new anxiolytics seems most promising?

There really isn’t enough data to compare these substances directly with one another to determine which is most promising. However, judging by the current statuses of each of the anxiolytics, it would appear as though Aloradine is a clear-cut favorite to get FDA approval simply because it is already in Phase III clinical trials. This doesn’t mean that it will necessarily end up making it to the market, but it likely has something going for it to already be in Phase III.

Following Aloradine, I think the prebiotic B-GOS is relatively exciting because it highlights a new modality of treating anxiety. As science continues to decipher the functions of gut bacteria, more prebiotic treatments will likely surface as a means to influence brain function as well as physical health.

Personal thoughts on the new anxiolytics

I like the method of administration for Aloradine, reminds me of a natural substance called “Rescue Remedy” that works fast. I also like the fact that more attention is being paid to gut bacteria and its potential to cause anxiety. I don’t think there are as many anxiolytics in development as there should be given the fact that the most effective drugs (e.g. benzos) are associated with addiction, dependence, and dementia.

When companies think outside the box to come up with unique treatments is what I like. The dogma that all cases of anxiety need to be treated with pills that target neurotransmitters can be put to rest. Unfortunately pharmaceutical companies have a tough time breaking free from the pill-to-target-a-specific-neurotransmitter paradigm. More attention needs to be paid to an individual from a holistic perspective rather than targeting one specific hormone, chemical, gut bacteria, etc.

There are an estimated 40 million people above age 18 that suffer from anxiety, while there are an estimated 350 million people that suffer from depression. Clearly more emphasis will be placed on coming up with treatments for the biggest societal burden that is depression.  Fortunately with new research surfacing all the time of things that may be linked to anxiety (e.g. translocator protein), more companies should continue to improve upon existing treatments.

Are you excited about any new anxiolytics in development?

Although it could be the case that none of these anxiolytics ever make it through clinical trials, I have a hunch that some will. If you are excited about any anxiolytic in particular, feel free to share your thoughts in the comments section below. Keep in mind that none of these drugs should be perceived as a panacea and most will likely still carry side effects.

Some people may not be impressed at all by these developments in the works for anxiety, and that’s fine. However, it’s important to realize that we can all easily act as critics on the lack of new developments for the treatment of anxiety. If you want to improve treatments for mental illness, then you may want to consider contributing in whatever way you are capable to make it become a reality.

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