A technology lab developing the next phase of human biology. https://human3.co
A technology lab developing the next phase of human biology. https://human3.co
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Cannabidiol, commonly known as CBD, has infiltrated the mainstream over the past decade, and its beneficial effects on the human body are now widely known.
Cannabinoids like CBD interact with the human body through the endocannabinoid system and noncannabinoid receptors, modulating brain functions like sleep and stress responses.
The purpose of this whitepaper is two-fold:
Explain the scientific mechanisms for the effectiveness of both standard CBD and Instant Hemp™, a nanotech CBD with particles 100x smaller than other CBD tinctures.
Explore how CBD affects the nervous system and other biological systems, and how nanoparticles from Instant Hemp™ can vastly improve the effectiveness and time it takes to feel these benefits.
Instant Hemp™ was designed for those that aim to substantively feel the subjective benefits of CBD – quickly:
Creatives
Biohackers seeking to optimize their sleep quality (falling asleep, staying asleep longer, and increasing Deep/REM sleep).
Psychedelic explorers
Athletes
Working professionals
Top use cases As reported by users from from beta testing.
Deep Sleep + REM sleep optimization
Falling back asleep in the middle of the night
Creative work – accessing divergent creative thinking
Socializing – a social lubricant that acts as an alternative to alcohol
Facilitating a soft landing from a psychedelic session
Recalibrating the nervous system from stressful events
Downshifting from an action-packed day into evening
A supplement can only have an effect if the body can absorb it.
Bioavailability—the rate and degree at which a substance enters the bloodstream—is crucial to creating CBD products that deliver proven benefits.
The bioavailability of CBD depends on several factors, including the method of consumption. If an individual receives CBD directly into the bloodstream (for example, via an intravenous bolus injection), bioavailability is, by definition, 100%. This means that CBD will exert its full effect.
Other methods, such as oral capsules, are less effective.
After oral administration, the amount of CBD that reaches the bloodstream depends on:
The particle's size
Ability to dissolve in water (hydrophilicity)
Ability to dissolve in oil (lipophilicity).
To apply its medicinal effect, CBD particles must be sufficiently hydrophilic to dissolve in body fluids at the site of absorption (e.g., under your tongue or in the gastrointestinal tract), but also sufficiently lipophilic to pass through cell membranes (made of two layers of lipid molecules).
Most CBD tinctures on the market are oil-based, lipophilic solutions.
Bioavailability from a regular oil-based capsule formulation of CBD was estimated to be as low as 6% due to poor ability to dissolve in water and significant hepatic first-pass metabolism.
Hepatic first-pass metabolism is a phenomenon of drug metabolism whereby the concentration of the active ingredient (in this case, CBD) is greatly reduced before it reaches systemic circulation.
In addition, standard CBD particles don’t get absorbed in the gut easily.
All these characteristics drastically reduce the bioavailability and therapeutic effects of CBD. So - theoretically, if you consume 150 mg of standard oil-based CBD, only 6% of it (9 mg) will arrive in your bloodstream to produce an active effect. This means that you may need a very large quantity of CBD to have a therapeutic effect.
Nanotechnology deals with dimensions less than 100 nanometers, which is 1,000 times smaller than the width of human hair.
We've applied the science of nanotechnology to improve the effectiveness of CBD 5-fold.
Breaking down CBD into nanoparticles accomplishes two things:
Increases solubility in water
increases surface-area-to-volume ratio.
Increased solubility in water allows the particles to absorb under your tongue and along the gastrointestinal tract, allowing them to reach the bloodstream.
The increased surface area in contact with the body's tissues greatly improves absorption.
The tiny particle size of the molecules allows them to effortlessly fit between the spaces in your cells, including the mucous layer in the mouth, and the gastrointestinal lining of the gut. Standard large CBD particles are unable to fit through the mucous layer.
Instant Hemp is taken sublingually. Its tiny particle size and ability to dissolve in water allow it to be absorbed through the mucous membrane in the mouth.
This gets the CBD to the bloodstream in minutes, avoiding the problems associated with digestion and first-pass metabolism. Ultimately, this produces a substantially higher concentration of CBD in the bloodstream.
Recent studies with nanoformulations have demonstrated this effect.
Atsmon and colleagues compared the bioavailability of Sativex® (an oromucosal spray with approximately equal doses of THC and CBD) to a CBD/THC nanoemulsion in healthy male volunteers. The authors reported several advantages of the CBD/THC nanoemulsion over Sativex®, including a faster rate of absorption and improved bioavailability.
Another study with healthy volunteers reported an improved absorption of a CBD/THC nanoemulsion containing piperine (an absorption enhancer) compared to Sativex®.
The central nervous system needs a highly controlled microenvironment to maintain proper neuronal functioning, and the blood-brain barrier (BBB) provides this function. It prevents neurotoxic molecules, blood cells, and pathogens from entering the brain.
At the same time, the BBB regulates the transport of molecules into and out of the central nervous system. This mechanism helps maintain the tightly controlled chemical composition of the neuronal milieu.
In the capillaries forming the BBB, endothelial cells are wedged extremely close to each other, forming so-called tight junctions. The tight gap allows only tiny particles, fat-soluble molecules, and some gases to pass through the capillary wall to enter the brain tissue.
Once CBD is absorbed into the bloodstream, it quickly crosses the BBB and accesses the central nervous system, as reviewed by Calapai and colleagues (2020).
The main advantage of Instant Hemp™ is the increased bioavailability compared with regular-sized particles of CBD. Its small particle size allows more CBD particles to reach the brain, faster.
Once in the brain, CBD affects the central nervous system by engaging different targets and acting through multiple molecular mechanisms.
A well-accepted set of targets include cannabinoid, opioid, and serotonin 5-HT1A receptors, the last one being closely related to its effects on mental health.
Studies have also shown that CBD directs the brain to activate the parasympathetic nervous system, which induces a state of calm. This is evident by an increase in heart rate variability induced by CBD. The greater heart rate variability (the variance in time between the beats of your heart), the more ready your body is to respond to various physiological and environmental stimuli, including stress.
CBD also increases brain GABA levels in neurotypical individuals. GABA is a neurotransmitter that helps to decrease the activity of neurons in the brain, which can reduce anxiety, promote feelings of relaxation and well-being. By increasing GABA levels in the brain, it is possible to promote sleep and improve sleep quality.
CBD alsoand boosts adenosine signaling, another mechanism that has beneficial effects in the context of sleep disturbances. Adenosine is known as ‘sleep pressure’ – an increase in adenosine drives the desire to fall asleep.
Furthermore, CBD modifies the activity of ion channels and enhances the activation of G protein-regulated receptors.
Several studies have shown CBD’s effect on anxiety, stress, and mental health:
A study conducted by Crippa and colleagues (2019) showed that healthy male subjects given oral CBD before a simulated public speaking test induced anxiolytic effects
A study conducted by Crippa and colleagues revealed that 400mg of CBD decreased neuronal activity in the limbic and paralimbic areas of the brain. The limbic and paralimbic brain areas comprise of a collective of structures involved in processing emotion and memory. The study suggests that the anti-anxiety effects of CBD are exerted through modulating the limbic and paralimbic areas of the brain.
A study by Masataka et al. showed that relative to placebo, 300mg/day of CBD for four weeks significantly reduced anxiety of participants with social anxiety and avoidant personality disorder
retrospective clinical trial that included any type of anxiety disorder, found that a dose of CBD (25 to 75 mg/day) was also effective for reducing anxiety
a 2022 review article reported that CBD had a positive effect against stress and its manifestations of fear, anxiety, depressive behaviors, or burnout.
a study with frontline healthcare workers during the COVID-19 pandemic reported that the anxiolytic effects of repeated CBD administration (300mg /day for 28 days) were maintained up to 1 month after the treatment discontinuation, suggesting a persistent decrease in anxiety in this group in the real world.
It's important to note that most of these studies used standard oil-based CBD formula, meaning its bioavailability was likely closer to 6%.
Although many recreational users of Cannabis will never face serious or permanent health deficits, it can still cause undesirable psychological side effects, including cognitive impairment, anxiety, paranoia, and an increased risk of developing chronic psychosis and addiction, especially with the daily use of Cannabis that is high in THC.
As reported by Andrew Huberman’s review of the literature on his Huberman Lab Podcast, other potential downsides of chronic Cannabis use are:
Changes in vocal effort, intensity, pronunciation of words, intonation, and anunciation.
Lowered libido.
Lowered testosterone.
Impaired sperm motility.
Anxiety or depression when not under the influence of Cannabis.
Several studies have reported that CBD can reduce the anxiety and psychosis-like effects that are seen after THC administration.
CBD attenuates the emotional and reward processing impairments associated with a single high dose of THC, as reviewed by Freeman et al. (2019). Although significant variability was reported in the effects of CBD and THC between studies and across individuals within studies, this review article suggests that CBD may weaken the effects of THC on emotion and reward processing.
The mechanisms by which CBD mitigates the side effects of THC have not been fully identified. A study with healthy volunteers showed that THC strongly disrupts striato-cortical networks, a well-integrated regulatory circuit that links the cortical and subcortical brain regions involved in cognition, attentional control, and motivation. The study also found that and the co-administration of CBD counteracts this effect.
In addition, preclinical evidence suggests that CBD prevents THC-induced behavioral and neural abnormalities by blocking its ability to overstimulate the ERK pathway in the hippocampus. Notably, the effects of THC on ERK in the hippocampus and their consequences on gene expression may be involved in the motivational aspects related to THC, including the rewarding effects.
Theorized mechanisms of why CBD tends to anecdotally enhance sleep architecture include increased adenosine and GABA signaling, reduced core body temperature (a tenet of deep restorative sleep), and reduced anxiety.
The increased productivity in studies of CBD actions is likely to accelerate and will provide essential neurobiological information about the mechanisms involved in the actions of CBD in sleep.
Most studies on the effects of cannabinoids in sleep have focused on purified THC or THC/CBD preparations. For example, experience to date with Sativex® in many Phase I-III studies demonstrates marked improvement in subjective sleep parameters in patients with various pain conditions, including multiple sclerosis, peripheral neuropathic pain, intractable cancer pain and rheumatoid arthritis, with no evidence of tolerance to the drug action and an acceptable adverse event profile.
A study conducted by Nicholson and colleagues (2004) reported mixed effects of combined THC and CBD, with THC generally increasing sedation and a low dose of CBD (15mg) having opposing, wake-enhancing effects. In fact, the administration of CBD has been shown to have differential effects on sleep based on dose. While low-dose CBD has a stimulating effect, high-dose CBD has a sedating effect. In a study among individuals with insomnia, administration of 160 mg/day of CBD increased total sleep time and decreased the frequency of arousals during the night, while low-dose CBD has been associated with increased wakefulness, as mentioned above.
A retrospective case series at a psychiatric clinic measured sleep and anxiety scores in 72 adults treated with CBD (25 mg/day to 175 mg/day). Anxiety scores decreased within the first month of CBD administration in 79.2% of patients and remained decreased for the duration of the study. Sleep scores improved within the first month in 66.7% of patients but fluctuated over time. Importantly, CBD was well tolerated in all but three patients.
Recent observations have suggested that CBD might represent an alternative treatment for REM sleep behavior disorder, which is a parasomnia characterized by the loss of muscle atonia during REM sleep associated with nightmares and active behavior during dreaming.
In a case series reported by Chagas and colleagues (2014), four patients treated with CBD had a prompt and substantial reduction in the frequency of REM sleep behavior disorder-related events without side effects. Likewise, a clinical study enrolling 33 patients with REM sleep behavior disorder and Parkinson's disease reported that CBD (300mg administered orally for 12 weeks) significantly improved the average sleep satisfaction from the 4th to 8th week of treatment compared to the placebo group.
Although further controlled research into the physiological effects of CBD is necessary, these studies suggest that a low dose of CBD could help manage excessive daytime sleepiness, while some cannabis formulations support sustained sleep improvement.
CBD is proving promising as a therapeutic for:
Reducing anxiety, stress, and fear
Improving Sleep Quality (through boosting GABA, Adenosine)
Activating the parasympathetic nervous system
Protecting against the adverse psychological effects of THC
Most standard CBD tinctures are poorly bioavailable, meaning you need to take megadoses to reach therapeutic effect, and wait 45-60 minutes to feel an effect.
Instant Hemp utilizes CBD nanoparticles for:
Rapid effect in the bloodstream
Increased bioavailability
Lower dose needed for therapeutic effect
Cannabidiol, commonly known as CBD, has infiltrated the mainstream over the past decade, and its beneficial effects on the human body are now widely known.
Cannabinoids like CBD interact with the human body through the endocannabinoid system and noncannabinoid receptors, modulating brain functions like sleep and stress responses.
The purpose of this whitepaper is two-fold:
Explain the scientific mechanisms for the effectiveness of both standard CBD and Instant Hemp™, a nanotech CBD with particles 100x smaller than other CBD tinctures.
Explore how CBD affects the nervous system and other biological systems, and how nanoparticles from Instant Hemp™ can vastly improve the effectiveness and time it takes to feel these benefits.
Instant Hemp™ was designed for those that aim to substantively feel the subjective benefits of CBD – quickly:
Creatives
Biohackers seeking to optimize their sleep quality (falling asleep, staying asleep longer, and increasing Deep/REM sleep).
Psychedelic explorers
Athletes
Working professionals
Top use cases As reported by users from from beta testing.
Deep Sleep + REM sleep optimization
Falling back asleep in the middle of the night
Creative work – accessing divergent creative thinking
Socializing – a social lubricant that acts as an alternative to alcohol
Facilitating a soft landing from a psychedelic session
Recalibrating the nervous system from stressful events
Downshifting from an action-packed day into evening
A supplement can only have an effect if the body can absorb it.
Bioavailability—the rate and degree at which a substance enters the bloodstream—is crucial to creating CBD products that deliver proven benefits.
The bioavailability of CBD depends on several factors, including the method of consumption. If an individual receives CBD directly into the bloodstream (for example, via an intravenous bolus injection), bioavailability is, by definition, 100%. This means that CBD will exert its full effect.
Other methods, such as oral capsules, are less effective.
After oral administration, the amount of CBD that reaches the bloodstream depends on:
The particle's size
Ability to dissolve in water (hydrophilicity)
Ability to dissolve in oil (lipophilicity).
To apply its medicinal effect, CBD particles must be sufficiently hydrophilic to dissolve in body fluids at the site of absorption (e.g., under your tongue or in the gastrointestinal tract), but also sufficiently lipophilic to pass through cell membranes (made of two layers of lipid molecules).
Most CBD tinctures on the market are oil-based, lipophilic solutions.
Bioavailability from a regular oil-based capsule formulation of CBD was estimated to be as low as 6% due to poor ability to dissolve in water and significant hepatic first-pass metabolism.
Hepatic first-pass metabolism is a phenomenon of drug metabolism whereby the concentration of the active ingredient (in this case, CBD) is greatly reduced before it reaches systemic circulation.
In addition, standard CBD particles don’t get absorbed in the gut easily.
All these characteristics drastically reduce the bioavailability and therapeutic effects of CBD. So - theoretically, if you consume 150 mg of standard oil-based CBD, only 6% of it (9 mg) will arrive in your bloodstream to produce an active effect. This means that you may need a very large quantity of CBD to have a therapeutic effect.
Nanotechnology deals with dimensions less than 100 nanometers, which is 1,000 times smaller than the width of human hair.
We've applied the science of nanotechnology to improve the effectiveness of CBD 5-fold.
Breaking down CBD into nanoparticles accomplishes two things:
Increases solubility in water
increases surface-area-to-volume ratio.
Increased solubility in water allows the particles to absorb under your tongue and along the gastrointestinal tract, allowing them to reach the bloodstream.
The increased surface area in contact with the body's tissues greatly improves absorption.
The tiny particle size of the molecules allows them to effortlessly fit between the spaces in your cells, including the mucous layer in the mouth, and the gastrointestinal lining of the gut. Standard large CBD particles are unable to fit through the mucous layer.
Instant Hemp is taken sublingually. Its tiny particle size and ability to dissolve in water allow it to be absorbed through the mucous membrane in the mouth.
This gets the CBD to the bloodstream in minutes, avoiding the problems associated with digestion and first-pass metabolism. Ultimately, this produces a substantially higher concentration of CBD in the bloodstream.
Recent studies with nanoformulations have demonstrated this effect.
Atsmon and colleagues compared the bioavailability of Sativex® (an oromucosal spray with approximately equal doses of THC and CBD) to a CBD/THC nanoemulsion in healthy male volunteers. The authors reported several advantages of the CBD/THC nanoemulsion over Sativex®, including a faster rate of absorption and improved bioavailability.
Another study with healthy volunteers reported an improved absorption of a CBD/THC nanoemulsion containing piperine (an absorption enhancer) compared to Sativex®.
The central nervous system needs a highly controlled microenvironment to maintain proper neuronal functioning, and the blood-brain barrier (BBB) provides this function. It prevents neurotoxic molecules, blood cells, and pathogens from entering the brain.
At the same time, the BBB regulates the transport of molecules into and out of the central nervous system. This mechanism helps maintain the tightly controlled chemical composition of the neuronal milieu.
In the capillaries forming the BBB, endothelial cells are wedged extremely close to each other, forming so-called tight junctions. The tight gap allows only tiny particles, fat-soluble molecules, and some gases to pass through the capillary wall to enter the brain tissue.
Once CBD is absorbed into the bloodstream, it quickly crosses the BBB and accesses the central nervous system, as reviewed by Calapai and colleagues (2020).
The main advantage of Instant Hemp™ is the increased bioavailability compared with regular-sized particles of CBD. Its small particle size allows more CBD particles to reach the brain, faster.
Once in the brain, CBD affects the central nervous system by engaging different targets and acting through multiple molecular mechanisms.
A well-accepted set of targets include cannabinoid, opioid, and serotonin 5-HT1A receptors, the last one being closely related to its effects on mental health.
Studies have also shown that CBD directs the brain to activate the parasympathetic nervous system, which induces a state of calm. This is evident by an increase in heart rate variability induced by CBD. The greater heart rate variability (the variance in time between the beats of your heart), the more ready your body is to respond to various physiological and environmental stimuli, including stress.
CBD also increases brain GABA levels in neurotypical individuals. GABA is a neurotransmitter that helps to decrease the activity of neurons in the brain, which can reduce anxiety, promote feelings of relaxation and well-being. By increasing GABA levels in the brain, it is possible to promote sleep and improve sleep quality.
CBD alsoand boosts adenosine signaling, another mechanism that has beneficial effects in the context of sleep disturbances. Adenosine is known as ‘sleep pressure’ – an increase in adenosine drives the desire to fall asleep.
Furthermore, CBD modifies the activity of ion channels and enhances the activation of G protein-regulated receptors.
Several studies have shown CBD’s effect on anxiety, stress, and mental health:
A study conducted by Crippa and colleagues (2019) showed that healthy male subjects given oral CBD before a simulated public speaking test induced anxiolytic effects
A study conducted by Crippa and colleagues revealed that 400mg of CBD decreased neuronal activity in the limbic and paralimbic areas of the brain. The limbic and paralimbic brain areas comprise of a collective of structures involved in processing emotion and memory. The study suggests that the anti-anxiety effects of CBD are exerted through modulating the limbic and paralimbic areas of the brain.
A study by Masataka et al. showed that relative to placebo, 300mg/day of CBD for four weeks significantly reduced anxiety of participants with social anxiety and avoidant personality disorder
retrospective clinical trial that included any type of anxiety disorder, found that a dose of CBD (25 to 75 mg/day) was also effective for reducing anxiety
a 2022 review article reported that CBD had a positive effect against stress and its manifestations of fear, anxiety, depressive behaviors, or burnout.
a study with frontline healthcare workers during the COVID-19 pandemic reported that the anxiolytic effects of repeated CBD administration (300mg /day for 28 days) were maintained up to 1 month after the treatment discontinuation, suggesting a persistent decrease in anxiety in this group in the real world.
It's important to note that most of these studies used standard oil-based CBD formula, meaning its bioavailability was likely closer to 6%.
Although many recreational users of Cannabis will never face serious or permanent health deficits, it can still cause undesirable psychological side effects, including cognitive impairment, anxiety, paranoia, and an increased risk of developing chronic psychosis and addiction, especially with the daily use of Cannabis that is high in THC.
As reported by Andrew Huberman’s review of the literature on his Huberman Lab Podcast, other potential downsides of chronic Cannabis use are:
Changes in vocal effort, intensity, pronunciation of words, intonation, and anunciation.
Lowered libido.
Lowered testosterone.
Impaired sperm motility.
Anxiety or depression when not under the influence of Cannabis.
Several studies have reported that CBD can reduce the anxiety and psychosis-like effects that are seen after THC administration.
CBD attenuates the emotional and reward processing impairments associated with a single high dose of THC, as reviewed by Freeman et al. (2019). Although significant variability was reported in the effects of CBD and THC between studies and across individuals within studies, this review article suggests that CBD may weaken the effects of THC on emotion and reward processing.
The mechanisms by which CBD mitigates the side effects of THC have not been fully identified. A study with healthy volunteers showed that THC strongly disrupts striato-cortical networks, a well-integrated regulatory circuit that links the cortical and subcortical brain regions involved in cognition, attentional control, and motivation. The study also found that and the co-administration of CBD counteracts this effect.
In addition, preclinical evidence suggests that CBD prevents THC-induced behavioral and neural abnormalities by blocking its ability to overstimulate the ERK pathway in the hippocampus. Notably, the effects of THC on ERK in the hippocampus and their consequences on gene expression may be involved in the motivational aspects related to THC, including the rewarding effects.
Theorized mechanisms of why CBD tends to anecdotally enhance sleep architecture include increased adenosine and GABA signaling, reduced core body temperature (a tenet of deep restorative sleep), and reduced anxiety.
The increased productivity in studies of CBD actions is likely to accelerate and will provide essential neurobiological information about the mechanisms involved in the actions of CBD in sleep.
Most studies on the effects of cannabinoids in sleep have focused on purified THC or THC/CBD preparations. For example, experience to date with Sativex® in many Phase I-III studies demonstrates marked improvement in subjective sleep parameters in patients with various pain conditions, including multiple sclerosis, peripheral neuropathic pain, intractable cancer pain and rheumatoid arthritis, with no evidence of tolerance to the drug action and an acceptable adverse event profile.
A study conducted by Nicholson and colleagues (2004) reported mixed effects of combined THC and CBD, with THC generally increasing sedation and a low dose of CBD (15mg) having opposing, wake-enhancing effects. In fact, the administration of CBD has been shown to have differential effects on sleep based on dose. While low-dose CBD has a stimulating effect, high-dose CBD has a sedating effect. In a study among individuals with insomnia, administration of 160 mg/day of CBD increased total sleep time and decreased the frequency of arousals during the night, while low-dose CBD has been associated with increased wakefulness, as mentioned above.
A retrospective case series at a psychiatric clinic measured sleep and anxiety scores in 72 adults treated with CBD (25 mg/day to 175 mg/day). Anxiety scores decreased within the first month of CBD administration in 79.2% of patients and remained decreased for the duration of the study. Sleep scores improved within the first month in 66.7% of patients but fluctuated over time. Importantly, CBD was well tolerated in all but three patients.
Recent observations have suggested that CBD might represent an alternative treatment for REM sleep behavior disorder, which is a parasomnia characterized by the loss of muscle atonia during REM sleep associated with nightmares and active behavior during dreaming.
In a case series reported by Chagas and colleagues (2014), four patients treated with CBD had a prompt and substantial reduction in the frequency of REM sleep behavior disorder-related events without side effects. Likewise, a clinical study enrolling 33 patients with REM sleep behavior disorder and Parkinson's disease reported that CBD (300mg administered orally for 12 weeks) significantly improved the average sleep satisfaction from the 4th to 8th week of treatment compared to the placebo group.
Although further controlled research into the physiological effects of CBD is necessary, these studies suggest that a low dose of CBD could help manage excessive daytime sleepiness, while some cannabis formulations support sustained sleep improvement.
CBD is proving promising as a therapeutic for:
Reducing anxiety, stress, and fear
Improving Sleep Quality (through boosting GABA, Adenosine)
Activating the parasympathetic nervous system
Protecting against the adverse psychological effects of THC
Most standard CBD tinctures are poorly bioavailable, meaning you need to take megadoses to reach therapeutic effect, and wait 45-60 minutes to feel an effect.
Instant Hemp utilizes CBD nanoparticles for:
Rapid effect in the bloodstream
Increased bioavailability
Lower dose needed for therapeutic effect
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