Picamilon is a synthetic compound made of GABA and vitamin B3 (niacin). It crosses the blood-brain barrier more easily than GABA alone, and has been claimed to potentially improve cognitive function and reduce anxiety. But what does the science actually say, and how much do we really know about this compound? Read on to learn more about picamilon, how it might work, and what we know about its efficacy and safety.
Disclaimer: This post is not a recommendation or endorsement for the use of picamilon. The FDA has not approved this compound for any specific medical or other use, and the available research on it is still in a very early stage. We have written this post for informational purposes only, and our goal is solely to inform people about what science currently says about picamilon’s potential effects, mechanisms, and side-effects.
What is Picamilon?
Picamilon (nicotinoyl-gamma-aminobutyric acid) is a synthetic combination of GABA and niacin (vitamin B3) that has been used by some in the past for the treatment of anxiety disorders, among other potential applications [1].
GABA is one of the major inhibitory neurotransmitters in the brain. Although its range of mechanisms and functions are complex, it has been generally associated with relaxing and anti-anxiety effects when its levels are increased [1, 2].
Niacin is a vitamin involved in DNA repair, fat and cholesterol synthesis, and the widening (dilation) of blood vessels.
Picamilon was first developed in the Soviet Union in the late 1960s and has been sold as a prescription drug for anxiety in Russia since the 1980s [3, 2].
Picamilon is not approved as a prescription drug in the United States. In 2015, the FDA ruled that picamilon can’t be sold as a dietary supplement because not enough is known about its effects or its safety, and subsequently ordered five different supplement companies to remove it from their products. However, there are still some companies based in the United States that sell it illegally. Additionally, a review of the available consumer versions of picamilon reported that the dosages can vary wildly from product to product – ranging from as little as 2.7 mg all the way up to over 700mg – and users cannot always be sure exactly what these supplements contain, which raises many major questions related to consumer safety [2].
Mechanism of Action
When taken as an oral supplement by itself, GABA is generally not able to cross the blood-brain barrier (only a small amount does). However, picamilon (i.e. a compound formulation in which GABA is bound to niacin) is believed to be able to cross the blood-brain barrier, which reportedly allows this particular formulation to affect the brain more readily and directly [4, 5, 6].
Picamilon’s reported ability to more readily cross the blood-brain barrier (BBB) is believed to be mostly due to the ability of niacin to widen blood vessels. Once picamilon enters the brain, the combined molecule is then broken down into its simpler components, GABA and niacin [6].
Once in the brain, GABA activates GABA receptors (both GABAA and GABAB types), while niacin may increase blood flow throughout the brain (by dilating blood vessels). By bringing fresh oxygen and other essential nutrients that nourish brain cells, this additional blood flow to the brain is believed to account for at least some of the purported neuroprotective and “nootropic” (“cognitive-enhancing”) benefits of picamilon – although more research will be needed to fully confirm this, as very little hard evidence regarding its effectiveness in human users is currently available [7].
Purported Uses of Picamilon
INSUFFICIENT EVIDENCE:
While some preliminary studies have investigated the potential use of picamilon in certain specific medical contexts, much of this research is still in a very early stage, and in most cases, it is not yet possible to come to any firm conclusions about its relative efficacy and safety in human users.
Therefore, the potential effects listed below are still considered to have insufficient evidence, and these findings should be taken with a grain of salt until further research work – including large-scale clinical trials in healthy human users – is performed.
1) May Treat Certain Vision Disorders
Two very preliminary studies in patients with vision disorders have suggested that picamilon may have potential future use in helping treat certain types of eye disease.
The macula is the center of the retina of the eye, where vision is sharpest. According to one prospective cohort study of 60 patients with macular degeneration, three months of picamilon supplementation was reported to improve visual acuity in some patients [8].
Central chorioretinal dystrophy is a hereditary retinal disorder that results in a progressive visual loss. One prospective cohort study of 48 patients with central chorioretinal dystrophy reported that picamilon improved the ability to distinguish shapes and colors (contrast sensitivity), increased peripheral vision, and reduced glaucoma severity [9].
While these early findings are promising, much larger-scale clinical trials in human users would be needed to confirm the potential application of picamilon in vision disorders, as well as to determine just how effective and safe it may be.
Animal And Cell Research (LACKING EVIDENCE):
The following potential uses of picamilon are based solely on animal- or cell-based studies, and are lacking evidence from any appropriate human trials so far. Therefore, these are only potential “launching-points” for future clinical studies in humans, and no solid conclusions can be made about these effects in human users until much more additional research is done.
2) May Affect Anxiety and Depression
GABA is the brain’s primary inhibitory neurotransmitter, and greater levels of this molecule have been generally associated with decreased levels of anxiety [1].
GABA’s main role in the brain is to slow down excitatory communication between neurons. Too little GABA can cause restless thinking, anxiety, and insomnia [10, 11].
When released, GABA reduces the firing rate of neurons by blocking the activity of glutamate, the brain’s primary excitatory neurotransmitter. Too much glutamate can contribute to feelings of anxiety, muscular tension, and even increased the risk of seizures. One of the (many) functions of GABA is to counteract these effects, which may account for its reported “anti-anxiety” or “calming” effects [11].
People with relatively lower levels of GABA have been reported to have a relatively higher likelihood of developing anxiety disorders, which has led some researchers to suggest that increasing GABA could offer a potentially effective approach for treating anxiety [1].
However, actual hard data on this use in humans is so far lacking, and what little evidence there is comes only from animal studies.
For example, according to one animal study, picamilon was reported to reduce anxiety- and depression-related behaviors in rats – supposedly by activating GABA receptors [12].
In other animal studies, picamilon was reported to suppress aggressive responses to startling stimuli and slowed down the animals’ orientation to such stimuli. This may suggest a diminished anxiety response, although this evidence is very indirect, and would need to be confirmed by a lot more studies [7].
3) May Affect Memory
While some people online claim that picamilon may have “nootropic” or “cognition-enhancing” effects, hard evidence in support of these claims is currently lacking.
Only a single animal study has investigated the potential of picamilon to enhance specific cognitive functions for far. According to one study in rats, picamilon was reported to improve both short- and long-term memory, as well as navigation ability [13].
4) May Protect the Brain
Some have proposed that picamilon may protect the brain and its cells from certain forms of stress and damage – but what does the actual science say?
According to one preliminary animal study, picamilon was reported to protect neurons from being overactivated to the point of death (excitotoxicity). This same study also reported that picamilon increased mitochondrial function in the brain cells of rats who have sustained brain trauma [14].
In one other animal study, picamilon was reported to protect the brain and immune cells of sleep-deprived rats – supposedly by preventing cell membrane damage and reducing oxidative stress [15].
However, because these findings have only been reported by animal studies, there is no guarantee that these same mechanisms will translate over to human users, and much more research would be needed to properly confirm these effects.
5) May Increase Blood Flow to the Brain
Picamilon has sometimes been prescribed by doctors in Russia to treat migraine headaches, and is believed to be effective for this condition due to its ability to open constricted blood vessels in the brain [16]. However, this effect and its mechanisms remain largely speculative, and have not been confirmed by sufficient clinical studies in human users to permit any solid conclusions about its efficacy.
According to just one animal study, picamilon was reported to increase blood flow in the brain more than both piracetam and vinpocetine – two so-called “nootropics” that are believed to increase blood flow to the brain [17]. However, this study is quite old (from 1989), and its findings have not been followed up on or otherwise confirmed by any subsequent studies.
6) May Help with Parkinson’s Disease
One very early investigational animal study has looked at the potential of picamilon to affect some of the brain systems that are believed to be related to the development and progression of Parkinson’s disease.
According to this single animal study, picamilon was reported to bring serotonin and dopamine up to near-normal levels, and may have also increased the uptake of dopamine in the brain in a rat model of Parkinson’s disease [18]. However, much more clinical research would be needed to investigate this further.
7) May Protect Against Nerve Inflammation
According to a single animal study, picamilon has been reported to reduce inflammation of the nerves (neuropathy) in diabetic rats [19]. Nonetheless, whether this effect would translate to humans – or even just to other animals without an underlying health condition like diabetes – cannot be determined until a lot of additional research is done.
Picamilon Side–Effects
Like any drug, picamilon has the potential to cause adverse side-effects, some of which could be potentially quite serious.
Importantly, because this compound has not been well-studied, there is not much data available regarding how safe it might be for human users, or how frequently it might lead to negative side-effects.
For this reason, we would strongly advise against experimenting with this compound until more data about its safety is available.
If you do make the personal decision to experiment with it, be sure to discuss it with your doctor first! Also make sure that he- or she is fully up-to-date about any other medications or drugs you may be taking, any pre-existing health conditions, or other lifestyle and dietary factors that could potentially impact your health. This is crucial because only your doctor has the appropriate medical expertise to help you properly manage the potential side-effects, adverse drug interactions, and other potentially negative outcomes from using relatively unknown nootropic compounds (although even then, its safety still cannot be guaranteed due to a lack of appropriate clinical and medical data).
Although only a very small amount of research on picamilon’s safety in humans has been done so far, the early work that does exists suggests that it is generally safe – or at least not obviously toxic [20, 6].
Some of the adverse side-effects that have been reported so far include [20, 6]:
- Headache
- Dizziness
- Nausea
- Skin flushing
At high doses, picamilon may lower blood pressure, which may be unsafe for those with already low blood pressure (hypotension) and other pre-existing cardiovascular conditions [21].
Drug Interactions
Because picamilon has not been well-studied, almost no hard evidence is available regarding its potential interactions with other medications or compounds.
However, based on what we know so far about its chemical structure and its underlying mechanisms, it is likely that picamilon could (at the very least) interact with other substances that affect GABA- or niacin-related mechanisms.
Therefore, any substance or drug that modulates the GABA receptors has the potential to alter the effects of picamilon (and vice-versa). Some of these substances include:
- Alcohol
- Barbiturates
- Benzodiazepines
- Nonbenzodiazepines, like Ambien
Similarly, potential drug interactions for niacin include [22]:
- High-dose aspirin
- Uricosuric agents
- Alcohol
Use During Pregnancy and/or Nursing
Picamilon has also not been tested – at all – for its potential effects on pregnancy or breastfeeding. Therefore, it is highly advised to avoid this drug altogether while pregnant or nursing until more is known.
Dosage
Note: The information in this section contains information about the dosages commonly used by some of the early studies that have been done on picamilon so far. The information below is not intended as a guide for personal use of picamilon, as adequate data about its potency, safety, or overall effects in healthy human populations is not currently available.
The dosages commonly reported by the few clinical trials that have been done on picamilon so far typically range from 10-300 mg once daily.
Some users report greater efficacy when taken with food to maximize absorption, although whether these subjective reports have any basis in actual biological mechanisms is not yet known.
Limitations and Caveats
Many of picamilon’s benefits have yet to be investigated outside of animal studies, and appropriate human trials are lacking.
Though the very small amount of preliminary research that has been done so far has reported some promising early findings, not nearly enough clinical trials have been done in human users – and as such, picamilon has not been officially approved for any medical or other use, and it cannot be recommended at this time.
