Neuroscientist Reveals Strongest Legal Compound for Relaxation & Sleep - Dr. Scott Sherr

Intro (0s)

• Dr. Scott Sherr has been a frequent guest on the channel, discussing various topics related to neurochemistry and neuroscience (0s).
• A new mushroom compound has gained attention for its unique effects and origins (6s).
• The compound's mechanisms and scientific explanations for its effects on the brain are of particular interest to the channel's audience (17s).
• Dr. Scott Sherr is invited to share his expertise on the compound, its effects, and the underlying brain mechanisms (15s).

The Origin & Folklore Behind the Mushroom (Christmas mythology) (24s)

• The Amanita muscaria mushroom has been around for thousands of years and has been used in shamanic ceremonies in places like Northern Europe and Siberia, where it grows under pine trees (29s).
• The mushroom's red and white cap is iconic and is thought to be the origin of Christmas colors, with depictions in various forms of media such as Alice in Wonderland and Super Mario Brothers (54s).
• The Amanita muscaria mushroom contains two compounds: agarine and ibotenic acid, with ibotenic acid being a prodrug of agarine (1m23s).
• Ibotenic acid is mildly neurotoxic and causes a psychedelic experience, but only if the mushroom is not fully dried (1m51s).
• In Northern Siberia, people would dry the mushroom and put it on pine trees, which is where the tradition of decorating Christmas trees originated (1m35s).
• Reindeer are known to eat Amanita muscaria mushrooms and have a psychedelic experience, which can make them appear to be "tripping out" (2m7s).
• In the past, herders would give reindeer the mushrooms to make them easier to domesticate and herd (2m29s).
• Shamans would dress up in red and white, like the mushroom, and enter homes through the chimney due to heavy snow in Siberia, which is where the idea of Santa Claus entering through the chimney originated (2m40s).
• Ibotenic acid causes a relaxed and possibly visual psychedelic experience, but it is not as intense as experiences caused by LSD or DMT (3m6s).

Agarin (muscimol) (3m15s)

• Agarin, also known as muscimol, is a non-psychedelic molecule that works on the GABA receptor in the brain, promoting relaxation and sleep, and is completely legal in the United States except for the state of Louisiana where it is prohibited to grow or possess Amanita muscaria mushrooms, the natural source of agarin (3m15s).
• Amanita muscaria mushrooms contain both agarin and ibotenic acid, a neurotoxic component that can cause nausea, vomiting, and diarrhea if ingested in excess, but agarin itself is not neurotoxic and supports the GABA system (3m36s).
• Agarin is a unique molecule that supports the GABA system in a profoundly cool way, and it is also known by another name, muscimol, or muscle Mo for short (4m3s).
• The only state in the United States where Amanita muscaria mushrooms are prohibited is Louisiana, but in all other states, it is legal to grow or possess them, although caution is advised when foraging for wild mushrooms (3m25s).

Agarin & GABA (4m16s)

• GABA (Gamma-Aminobutyric Acid) is a crucial neurotransmitter in the brain, responsible for calming down the nervous system, and it takes about 20% of the brain's neurotransmission (4m32s).
• GABA receptors are found in various parts of the brain, particularly in areas responsible for sensory gating, which helps process and integrate motor and sensory information (4m51s).
• The GABA receptor itself is composed of five subunits that change depending on the location in the brain, with some subunits focused on anxiety relief, stress relief, visual representations, and sensory gating (5m17s).
• Sensory gating refers to the brain's ability to filter out irrelevant sensory information and focus on what's important, and GABA receptors play a crucial role in this process (5m31s).
• The GABA receptor has multiple binding sites, including the main GABA site where GABA binds, as well as other sites where substances like kava, magnolia bark, and valerian root can bind (6m2s).
• Agarin is unique in that it binds exactly to the GABA site on the GABA receptor, which is rare for other plants and substances (6m22s).
• GABA receptors are involved in various functions, including rest, relaxation, digestion, recovery, detoxification, and learning, and are found in areas of the brain responsible for processing and integrating information (4m29s).

Why Some People Feel Bad After Taking Valerian Root (6m33s)

• Some people may feel bad after taking valerian root due to its strong binding affinity to the GABA receptor, which can lead to a crash or rebound effect, causing hyper anxiety (7m29s).
• Valerian root binds to the benzodiazepine site on the GABA receptor, increasing the affinity for GABA to bind, which can prevent the firing of neurons and lead to relaxation (7m7s).
• Long-term use of valerian root and other non-pharmaceutical compounds like kava and honokiol can deplete GABA and downregulate GABA receptors, leading to tolerance and potential negative effects (7m54s).
• Depleting GABA can cause hyper irritability, increased stress, anxiety, depression, and sleep problems due to an imbalance with the excitatory neurotransmitter glutamate (8m50s).
• Downregulating GABA receptors can change an individual's baseline, requiring more GABA to achieve the same effect, similar to insulin resistance (9m14s).
• Agarin, a compound that can prevent GABA depletion and receptor downregulation, has the potential to mitigate these negative effects when taken with other substances that bind to the GABA receptor (8m32s).
• Agarin can be used to prevent GABA depletion and receptor downregulation when taken with substances like honokiol, which binds to the GABA receptor (8m36s).
• A product called Troy, available at TRscriptions, utilizes agarin and has been found to be effective in promoting relaxation and sleep (9m50s).

10% off Troscriptions (10m10s)

• Troscriptions is a company offering a unique blend of compounds to help with falling asleep and staying asleep, and a link to their website is provided in the video description (10m10s).
• Troscriptions offers various products, including Troom, which helps with relaxation, and Troz Plus, among others (10m33s).
• The particular compound used in their product contains a small dose of Melatonin, as well as Agarin, a unique compound derived from a mushroom, which helps users stay asleep and avoid waking up in the middle of the night (10m47s).
• The compound also includes Adenosine, which creates sleep pressure and helps individuals fall asleep (11m1s).
• Adenosine is a naturally occurring substance that builds up in the body, creating sleep pressure, such as after engaging in physical activity like running 10 miles (11m5s).
• The compound works differently from other sleep compounds and utilizes a unique delivery system, where it is absorbed quickly through the gum (11m17s).
• The science behind the compound and its effects will be discussed later in the episode with Dr. Scott Sherr (10m28s).

Obligate Pair - Agarin & Honokiol (11m28s)

• Agarin and Honokiol form an obligate pair, a combination that is very powerful for relaxation and sleep, with Agarin binding to the GABA receptor and Honokiol binding to the alisic site outside of where GABA would bind on the receptor (11m37s).
• Agarin is a long-acting compound with a half-life of 6.5 to 7 hours, making it suitable for use in sleep aids (12m0s).
• The combination of Agarin and Honokiol is used in a product called Troy, which also contains other ingredients such as 5-HTP, melatonin, and Denine to help augment sleep patterns (12m3s).
• Denine and Corpin, a compound from a zombie-fying mushroom, are also included in Troy to increase deep sleep by working on the adenosine system (12m26s).
• The key to the Troy formula is its ability to relax the user by modulating the GABA system in an obligate way, binding to the GABA receptor alisic with Honokiol and on the actual site where GABA would bind with Agarin (12m44s).
• The formula hits fast, with effects noticeable in as little as 10 minutes, and creates a feeling of readiness for sleep due to the adenosine system (13m1s).
• The long-acting GABA agonist Agarin helps regulate sleep, allowing users to wake up and go back to sleep, and reduces hyper-responsiveness and stimulation (13m19s).
• The half-life of Agarin is approximately 6.5 hours, allowing for flexible dosing, and the average dose of Troy is about 0.5 milligrams, a very small amount (14m0s).
• Other products using Agarin are being developed due to its powerful effects, and a link to Troy is provided for those interested in trying it out (14m19s).

Practical Applications of Agarin (14m38s)

• Agarin has potential applications beyond sleep aid, such as helping individuals who are "high-strung" or need to stay calm during workouts, by downregulating the nervous system and promoting relaxation (15m0s).
• Upregulating the GABA system with agarin can lead to increased relaxation and potential fatigue, requiring strategies to mitigate this effect (15m12s).
• Modulating the GABA system can improve performance and thinking in individuals who are highly stressed, as seen with the use of gabatone (15m27s).
• A compound called troom, which contains nicotin GABA, is being used to modulate the GABA system and has a mild activating effect due to its vitamin B3 component (15m43s).
• When using agarin during the day, smaller doses (e.g., a quarter of a milligram or less) are likely to be given to avoid excessive tiredness, making it challenging to source and formulate (16m3s).
• The company had to source agarin from outside the United States and manufacture it themselves after working with various labs and growers (16m19s).
• Dr. Ted Aoso, a pioneering pharmacologist and formulator, plays a key role in developing new compounds and formulations, including agarin, in his "kitchen lab" (16m36s).
• The company, consisting of four physicians, prioritizes safety, clinical relevance, and cleanliness in their products before releasing them to the public (16m53s).

How Caffeine Affects the GABA System (17m3s)

• Caffeine affects the GABA system by desensitizing it, resulting in reduced GABA tone for the amount of GABA present, even if the actual amount of GABA remains the same (17m14s).
• Consuming large amounts of caffeine over an extended period can lead to downregulation of GABA receptors, similar to the effects of benzodiazepines and other substances (17m30s).
• This downregulation of GABA receptors can contribute to irritability during caffeine withdrawal, which is not solely due to the need for energy (17m48s).
• Irritability is often caused by an imbalance of glutamate and GABA, with an overabundance of glutamate typically leading to irritability, tremors, and feelings of instability (17m56s).
• A rare occurrence is having too much GABA, which can happen when taking substances that increase GABA levels, resulting in the opposite effects of insomnia, depression, and anxiety (18m19s).
• A balance between glutamate and GABA is essential, as they account for 80% of neurotransmission, with the remaining 20% consisting of other neurotransmitters like serotonin, norepinephrine, and dopamine (18m38s).

5-HTP (18m49s)

• Serotonin is primarily produced in the gut, with 95-99% of it being made there, rather than in the brain (19m50s).
• The amount of serotonin in the gut can affect how sensitive someone is to taking serotonin, as the gut also contains neurons that can influence feelings of sleepiness in the brain (20m1s).
• 5-HTP is a precursor to serotonin that can cross the blood-brain barrier, but some people may be resistant to it due to issues with a transporter in their stomach (20m25s).
• Taking high doses of 5-HTP can cause apathy and extreme tiredness in some individuals, who are referred to as "hyper responders" (19m17s).
• People who take SSRIs often experience similar side effects, such as apathy and decreased motivation, due to serotonin overdrive (19m35s).
• Low doses of 5-HTP, combined with other ingredients, can be effective in promoting relaxation and sleep without building up tolerance or causing withdrawal symptoms (21m24s).
• A small amount of 5-HTP, such as 50 milligrams, can be sufficient for some people, and taking a fraction of this dose can still be effective (21m6s).
• The combination of 5-HTP and melatonin can be particularly effective in promoting relaxation and sleep (21m32s).
• The concept of biohacking involves experimenting with different combinations of substances to achieve a desired effect, and some individuals may choose to combine various compounds to create a synergistic effect (21m40s).
• Agrin is a parasympathetic activator, which means it promotes rest, recovery, digestion, and detoxification, and many people could benefit from incorporating it into their lives to counterbalance the constant "on" state of modern life (22m18s).
• When in a parasympathetic state, the body is able to rest, recover, digest, and detoxify, and agrin can help facilitate this state (22m22s).
• Some people may be skeptical about the effectiveness of 5-HTP due to concerns that it does not cross the blood-brain barrier, but anecdotal evidence suggests that it can still have a profound impact on the brain, possibly due to the gut-brain connection (22m43s).
• The gut microbiota plays a crucial role in signaling to the brain, and substances like 5-HTP may exert their effects indirectly through this connection (23m2s).
• Supplementation with certain compounds can be beneficial for overall health and well-being, and individuals may want to consider incorporating them into their regimen (23m21s).

Glutamine (23m25s)

• Glutamine supplementation is recommended, particularly for individuals who train hard, to support the Jaa system and potential influences from other compounds, with a suggested dosage of 2-5 grams. (23m25s)
• Glutamine is converted into glutamate in the brain, and glutamate is then converted into GABA, requiring a good source of glutamine for this process. (23m42s)
• Minerals such as magnesium and vitamin B6 are necessary co-actors for the conversion of glutamine to glutamate and glutamate to GABA. (23m50s)
• Having these co-actors present enables the efficient conversion of glutamine to glutamate and glutamate to GABA. (23m54s)
• To effectively relax, it is essential not to eliminate GABA too quickly and to engage in activities such as breath work, exercise, and increasing BDNF, which helps balance the GABA system. (24m0s)
• Exercise can aid in achieving a balance in the GABA system, and increasing BDNF can also enhance GABA levels in the brain. (24m6s)
• While compounds can be used to enhance the GABA system, it is also possible to achieve this naturally through various methods. (24m16s)

Thomas' Current Sleep Stack (24m25s)

• A nightly routine involves taking theanine, tryptophan, and 12-HDP every night (24m28s).
• Theanine is part of the nightly routine, but the specific dosage is not mentioned (24m28s).
• Tryptophan is also taken every night as part of the routine (24m28s).
• 12-HDP is taken every night, but the dosage is not specified (24m33s).
• Trzy is taken every third night or so to provide an extra sleep drive (24m37s).
• Sundays require an extra sleep drive, especially after pushing hard, which is why Trzy is taken (24m41s).
• The routine is necessary to meet the required sleep needs (24m41s).

Rutaecarpine (24m50s)

• Rutaecarpine is a compound that has been recently explored for its potential benefits in relaxation and sleep, and it is currently being researched for its supply side (24m50s).
• The compound works by upregulating S1P1A2 and S1P2E1, which can help counteract the effects of caffeine on sleep, as caffeine blocks adenosine receptors and Rutaecarpine can increase adenosine to compete with caffeine (25m30s).
• Adenosine is a short-acting compound when taken orally, but Rutaecarpine can help increase its effects to break off caffeine blockage and increase sleep drive (25m47s).
• Rutaecarpine has been tried on days with caffeine consumption past 11 am, and it has shown to be effective in promoting relaxation and sleep (25m26s).
• However, there are concerns about the long-term effects of Rutaecarpine, such as potential downregulation of receptors in the liver, making it harder to metabolize caffeine (26m1s).
• The body has feedback mechanisms to regulate receptors, hormones, neurotransmitters, and gut microbiota, which can be affected by compounds like Rutaecarpine (26m33s).
• More research is needed to understand the effects of Rutaecarpine on the body and its potential benefits and drawbacks (26m19s).

Where to Find More of Dr. Sherr (26m46s)

• Dr. Scott Sherr emphasizes the importance of maintaining a healthy respect for the feedback system, suggesting the use of low doses and cycling substances as a good idea (26m50s).
• To find more information, Dr. Scott Sherr can be found at transcription.com (26m56s).
• Dr. Scott Sherr is also active on Instagram, where he can be found under the handle @DrScottDSherr (27m0s).