Fear and worry associated with anxiety disorders impair normal daily activities and result in both psychological and physical symptoms, such as trembling and sweating. 

SSRIs and SNRIs are preferred as treatment for anxiety disorders but take 4 to 8 weeks to take effect. During this period, benzodiazepines can help augment treatment before SSRIs or SNRIs start working. Nevertheless, only 50% of patients respond to such treatment, with only one-third achieving remission. 

Here are some compounds under investigation.

 

Cholinergic modulation

 

BNC210 is a novel negative-allosteric modulator of the alpha-7 nicotinic receptor that has been studied in social anxiety disorder, generalized anxiety disorder, and PTSD. Early research has shown that this agent is effective in humans and is not linked to the adverse effects typically associated with anxiolytics. It is currently in phase 2 trials.

Hampsey E, Perkins A, Young AH. BNC210: an investigational α7-nicotinic acetylcholine receptor modulator for the treatment of anxiety disorders. Expert Opin Investig Drugs. 2023;32(4):277–282.

 

 

According to the authors of a 2023 review, “The currently available data indicate that BNC210 is a good candidate for both an effective and tolerable treatment, albeit this requires replication in larger studies. Ultimately, whilst there is cause of optimism, there is also insufficient data to yet suggest BNC210 constitutes a ‘leading’ candidate with respect to other novel treatments under development for anxiety disorders. If the encouraging results concerning efficacy and tolerability available so far are repeated in larger trials then BNC210 may well end up as a licensed treatment for anxiety disorders, albeit it is unclear if this would be in a stand-alone role or as an augmentation to available therapies.”

 

Fasedienol nasal spray

 

Moving forward, investigators plan to test the drug over several weeks, administered on an as-needed basis in patients with anxiety.

Ernst D. Fasedienol nasal spray reduces anxiety symptoms in patients with SAD. Medical Professionals Reference (MPR). August 7, 2023.

 

 

The magic in mushrooms

 

Psilocybin is found in psychedelic mushrooms and was first studied in the treatment of psychiatric illness in the mid-1900s. This research stopped due to its class I scheduling by the Controlled Substance Act of 1970. Although the FDA eventually allowed research on psychedelics to resume in 1992, there is still little research on the use of adjunctive psilocybin and psychotherapy in psychiatric illness, particularly PTSD.

Psilocin is the active ingredient in psilocybin and an agonist of the 5HT-2A, 5HT-2C, and 5HT-1A receptors; the 5HT-2A receptor mediates the drug’s hallucinogenic effects.

A limited number of clinical trials have demonstrated that psilocybin is relatively safe, with mild adverse effects such as headache, nausea, fatigue, and hypertension. It has been shown to decrease depression and anxiety in patients with life-threatening cancers in clinical trials. 

“Overall, the side effects of psilocybin administration are relatively mild and acute indicating that there is low potential for long-term adverse effects from psilocybin,” wrote the authors of a review published in Cureus.

Elsouri KN, Kalhori S, Colunge D, et al. Psychoactive drugs in the management of post traumatic stress disorder: a promising new horizon. Cureus. 2022;14(5):e25235.

 

 

 

5-HTP

 

Available as a drug and in supplements, L-5-hydroxytryptophan (5-HTP) is produced from tryptophan via tryptophan hydroxylase (TPH). Decarboxylation of 5-HTP produces serotonin (5-hydroxytryptamine, or 5-HT), which can then be transformed into melatonin (N-acetyl-5-methoxytryptamine). 5-HTP is important in neurologic and metabolic disease, with its synthesis from tryptophan representing the limiting step in serotonin and melatonin biosynthesis.

 

“The antidepressant activity appears to be linked to the activation rather than suppression of monoaminergic activity; therefore, the decreased monoamine metabolism found in some types of depression is likely to depend on a primary metabolic deficit rather than receptor hypersensitivity,” wrote authors in the International Journal of Molecular Sciences.

Maffei ME. 5-Hydroxytryptophan (5-HTP): natural occurrence, analysis, biosynthesis, biotechnology, physiology and toxicology. Int J Mol Sci. 2020;22(1):181.

“Decreased serotonergic activity may be present in both depression and mania and the therapeutic effect of 5-HTP has been correlated with an increase in serotonin at central serotonin receptors.”

 

In humans, 5-HT may be involved in the pathogenesis of anxiety. The administration of 5-HT leads to a moderate decrease in anxiety symptoms of agoraphobia and panic disorders.