Many compounds, particularly older ones developed in other countries (e.g., during the Soviet era or in Europe), remain unapproved by the FDA in the US primarily because they are off-patent or never patented in a way that allows pharmaceutical companies to recoup the high costs of clinical trials and approval processes through exclusivity. Without patent protection, there's little financial incentive for companies to invest in the expensive FDA-required studies, even if the drugs have demonstrated efficacy elsewhere and are approved for use in those regions. These are often sold as supplements in the US (with varying legality and safety warnings) or remain unavailable as prescription medications. Below is a list of examples, focusing on those with documented high efficacy in approved uses abroad, similar to Phenibut (which is approved in Russia, Latvia, and Ukraine for anxiety, insomnia, and neurological conditions, with studies showing effectiveness in reducing anxiety and improving sleep).

• Piracetam: A nootropic developed in Belgium, approved in over 100 countries (including much of Europe, Latin America, and Asia) for treating cognitive impairments, myoclonus, and post-stroke recovery. Clinical studies abroad show it improves memory and cognition in elderly patients and those with brain injuries, but no US company has pursued FDA approval due to its off-patent status since the 1970s.
• Aniracetam: Approved in Japan and parts of Europe for anxiety and cognitive disorders. Research in those regions indicates high efficacy in enhancing memory and reducing anxiety symptoms, often outperforming placebo in trials, but it's unapproved in the US and lacks patent-driven investment.
• Picamilon: A Russian-developed compound approved there and in Ukraine for cerebrovascular disorders, migraines, and anxiety. Studies show it effectively improves cerebral blood flow and reduces asthenia, but it's banned as a supplement in the US and not pursued for approval due to no profitability from patents.
• Vinpocetine: Derived from the periwinkle plant, approved in Europe, Japan, and China for cognitive decline and stroke recovery. Clinical data from those countries demonstrate efficacy in improving memory and cerebral circulation, with some studies suggesting it outperforms certain FDA-approved alternatives for vascular dementia, yet no FDA approval due to off-patent economics.
• Tianeptine: Approved in France, several Asian countries, and parts of Latin America as an antidepressant. International trials show it has high efficacy for major depressive disorder, often with fewer side effects than SSRIs, and it's particularly effective for anxiety comorbid with depression. It's off-patent and thus lacks US incentives for trials.
• Meldonium: Approved in Latvia, Russia, and other Eastern European countries for treating ischemia, heart conditions, and improving athletic performance recovery. Studies abroad indicate it enhances energy metabolism and reduces fatigue in cardiac patients, but it's not FDA-approved and was even banned by WADA for sports use, with no patent incentives driving US development.
• Omberacetam (Noopept): A Russian nootropic approved there for cognitive enhancement and neuroprotection. Research shows high efficacy in improving memory and reducing cognitive deficits post-trauma, often cited as more potent than piracetam, but unapproved in the US due to similar economic barriers.

Note: This list is not exhaustive and focuses on synthetic or semi-synthetic compounds with strong evidence from foreign approvals and studies. Herbal examples (e.g., Kava for anxiety, approved in Germany) face similar issues but are often regulated differently. Efficacy claims are based on international data, but these substances can have risks, and self-use without medical supervision is not recommended.