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. UPDATE: A newer article entitled “New Anxiety Medications 2018” has been published discussing anxiolytics in clinical trials.
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
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.”
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
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.
I think if they put these “Doctors” on Benzos at the same time they put panic patients and got them addicted to Benzos, we would be able to get FDA or government approval to remove them from the market. They are poison. We will never find anything to solve the problem because big pharma does not care and Dr’s are clueless or do not care about the addictive properties of what they are dishing out like gumdrops.
Just find a drug that turns off the amygdala! Jeez how hard can it be? Send people to the moon, nuclear bombs that can flatten cities with a 30 mile radius but can’t make a drug what can go to the root of the problem and turn off an overactive amygdala? What are these people doing? Stop flooding the whole brain with chemicals what we don’t need that’s just masking the problem, don’t mess around with chemicals of the stomach – that’s got nothing to do with it…. Just find a drug that turns down or off the amygdala!
Aloradine and the others all sound very promising, I just wonder how long it will be before we see any use of these in general psychiatric situations. Has anyone an idea of how to follow the research?
MDMA, LSD and the active ingredient in magic are being looked at now and from what I know they all seem promising. MDMA is being predicted to be FDA approved in less than five years and I know there’s another drug on trial that mimics ketamine but without the effects is looking priming too. It’s nearly 2017 for gods sake, its about time that one decent medication specifically for anxiety disorders is released. Imagine medications like prozac that were released in the 50s are still being used in 2016, it just goes to show how little they really know about the biological reasons for mental illnesses like depression and anxiety disorder.
Please explain what you meant by “Active ingredient in Magic”.
Totally agree with you mate, makes you wonder where they spend all the money… oh yeah, on pointless wars costing over 6 trillion! While millions suffer in this country alone needlessly, and in nearly 70 years, they have not made a drug that directly deals with anxiety, truly pathetic! Nice to know the money’s being put to good use.
I wish there was some medication that would assure me I won’t suffer from panic attacks anymore. It’s ok for me to be a little anxious during the day, but the fear of having a panic attack makes me being too careful about thinking too much, doing too much, being by myself and my life gets very limited. I want my freedom back because I know I can do well in life if I can control this.
I wish they would make a pill with the same ingredients that are in the Norco’s or pain pills, because they are the only thing that works for some people’s high anxiety. I would like to see them formulated to where they were allowed to be used for really bad people. It does work, but because of bad rap and people abusing them, it would be a miracle to see it.
I really hope Aloradine can help for agoraphobia, I hope it gets approved by the FDA.
I would certainly hope something of substance re: anxiety disorder is on the NEAR horizon, but with the FDA bureaucratic quagmire I can’t get my hopes up, unfortunately.
I am interested in trying all of them except number 5. Not at the same time, of course. I wonder if these drugs really will be made or if it’s just a scam. I am hoping these will get rid of my anxiety. There is no cure for anxiety, but if this is true about the medication, when will these medications be in the market and out for the public and available?
Gabapentin works okay for anxiety as an off label use, but after almost 2 years of taking highest dosage allowed, it has lost some of its effectiveness.
I suffer from severe agoraphobia and panic disorder, I really hope B-GOS makes it to the market. Benzos are horrible.
I am interested in S32212. I suffer from genetic anxiety and depression. The condition in my family can be traced back to my great grandmother and forward to my son. I am no expert but, it seems that the amount of serotonin in my family’s brain needs to be sufficient in order to process thoughts in a normal fashion. There appears to be no flaws in our emotional spectrum (autism) or aggression.
Furthermore, the SSRIs seem to work for my family as long as the dosage is correct. Too little SSRI causes drowsiness and lack of libido. Too much SSRI causes jitters and problems with concentration. Regardless of the SSRI dosage, our metabolism seems to slow down and calorie intake needs to be decreased. It sounds like S32212 might aid the amygdala and hippocampus without causing the side affects of SSRIs.
After suffering General Anxiety Anxiety disorder for 5 years following 2 treatments for cancer my reaction to the GAD has been worse than the cancer. My previous life has been altered beyond belief. There is not a day that goes by that I don’t deal with anxiety that has eliminated the active life I lead. I’ve tried every SSRI & SNRI as well as off label meds that’s made things worse.
If not for benzodiazepines I’d have no fruitful life at all. I surely would hope for new meds but given the way FDA works I’m not looking any time soon. I’ve additionally tried 4 years of psycho babble with minimal effect, except CBT… So Benzo is my only alternative and for that I’m thankful, until of course, the DEA makes it more difficult to obtain because of the failure of the “ill fated war on drugs” and puts the emphasis on abusers and disregards those who are helped.
I really hope the Aloradine gets approved. I like the idea of a nasal mist instead of a pill.
I hope that Aloradine (PH94B) also be used to treat Panic disorder.
The life I could lead, if I only I didn’t suffer with anxiety, I’m sure would be soooooo much more productive, not to mention happy.
Jane, I feel the same way. Anxiety has been a plague for me for too long. I don’t like taking benzodiazepines due to the addictive qualities.
That is exactly the situation I am in. Nothing works except for benzodiazepines. I am so desperate for anything else that works on anxiety!
I would like to see one that doesn’t affect your weight, doesn’t give you dry skin, and doesn’t mess with your thyroid.
Man I’m up for anything, I have a question why is it that my pain medication (norcos) works better for my anxiety than anything else I’ve tried. Are there any studies related to that? If so please point me in that direction… Thank you and I wish you all luck because I don’t think people take our diagnosis seriously and it’s such a hard thing to live through.
Anxiety rules my life. Kenny B, I have pain meds that I swear make everything better. Not buzzed or messed up. Just the only real relief with my anxiety and depression. I often worry about addiction. But if they work does that matter. I don’t know. I never heard anyone bringing this up so it makes me feel not alone.
You may have an endorphin deficiency (can cause anxiety and depression). For this there is the harmless supplement D-phenylalanine, which works by slightly preventing the breakdown of endorphins in the blood (remember, endorphin means endogenous morphine). Since endorphins bind to opioid receptors, it’s essentially the same as taking pain killers.
Perhaps Aloradine can also be used to treat OCD anxiety!
I’d really like to read more about emapunil, looks promising for me.
For the love of god I hope Aloradine works and get approved ASAP. I suffer with social anxiety and im tired of being drugged out of my mind by psychiatrists who genuinely dont have a clue what there doing. I told my last doc that I had enough of SSRIs after another year of failure, she told me that I would fall apart mentally if I did and tried to coax me into saying I was suicidal even though I wasnt and never claimed to be. Amazingly I have since read that people with social anxiety disorder produce too much serotonin which they now believe actually causes anxiety. I think I’ll go to a vet in future
Serotonin reuptake inhibiting drugs work by desensitizing serotonin receptors. It is essentially like stabbing a burn victim for weeks to get him to lose his pain caused by the burn. What you need is not an SSRI but an SSRE, a reuptake enhancer.
I’m excited about them all! I can’t tolerate SSRI’S or SRNI’s so an reliant on using sedatives when I need them to control my panic and anxiety. I am open minded and willing to try almost anything to have long term relief from the strong physical symptoms that I feel. Well done science! Keep trying please!
I am looking forward to ALKS-5461. Preliminary test results are very promising for the treatment of depression and the FDA has given it top priority to receive fast approval, possibly in 2016.