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Written by: Dr. Jonny Lisano, Ph.D.

Photo by Nik Shuliahin on Unsplash

Anxiety, we all experience it and deal with these feelings daily. It doesn’t matter if it’s a big presentation at work, getting ready for a first date, or worrying how others will judge your clothing choices. Stress from anxiety can manifest itself in many forms, but could cannabidiol (CBD) make these feelings more manageable? 

Anxiety

Anxiety is a broad term, and many different clinical conditions and everyday feelings can fall under this umbrella. It is defined as an intense, persistent and excessive feeling of worry or fear. These feelings of anxiousness can be evoked by both the fear of past experiences and the fear of new situations. For example, you might be terrified of public speaking because the last time you spoke in front of people you didn’t perform well, or you might be going out on a first date with someone you really like and are nervous about how the date will go.  There is no one-way anxiety manifests itself, and it varies from person to person. In our busy, modern-day world, it seems that anxiety is a regular, albeit unwanted, part of life.  

When we start to feel anxious this activates our sympathetic nervous system, which you have probably heard it more commonly referred to as the “fight or flight” response. When this system is activated, you have a heightened sense of alertness because your body is under the impression that it is in danger. Even though the stimuli, like public speaking, might not be physically threatening, it can be emotionally threatening, and evokes the same physiological response as being confronted with an angry bear.  Normal symptoms of anxiety can manifest as increased heart rate, rapid breathing, sweating, nausea or in severe cases loss of consciousness. These are all common responses to a stress-inducing situation.

A 2018 cross-sectional study of CBD users found that anxiety was the 3rd most common use for CBD, behind chronic pain and joint/arthritis pain (Corroon 2018).  Is this because it’s just a common disorder that people are seeking relief from, or is there some scientific merit to seeking cannabinoids to balance our emotional state? Let’s find out!

The Research on CBD

In 2016, a study was published by a research group investigating the effectiveness of orally ingested CBD oil for the treatment of anxiety, related to post-traumatic stress disorder in a 10-year old girl.  For this study they had the patient consume 6-12 mg of CBD at a time sublingually (under the tongue) as needed to treat her feelings of anxiety. Within the first 2-months, the patient’s SCARED score (a validated method to assess anxiety disorders in children) decreased from 34 to 24. On this index, a score greater than 25 indicates a high probability of an anxiety disorder. At the end of the treatment period, the participant’s SCARED score was down to 18. She was still taking 6-12 mg of CBD as needed for anxiety but was not having to consume it as often throughout the week as compared to earlier in the study (Shannon 2016).  Even though this was a case study observing one single participant, the results are promising, but do these findings still hold true in studies with a larger and more varied population?

Social anxiety disorder, also known as SAD, is a social phobia where the individual suffering from this condition experiences intense feelings from the fear of being judged, seen in a negative light or socially rejected by their peers and the public. A recent publication from Japan explored the effectiveness of CBD oil to treat symptoms of SAD in 37, 18-19-year-old teens living in Japan.  They were randomly assigned to either the control group or the experimental group, which received daily doses of 300 mg of CBD for four weeks. Participants were evaluated before and after the 4-week intervention using two separate measures of social anxiety. Compared to the placebo group, the teens that received treatment with CBD had a significant reduction of their scores on both the “Fear of Negative Evaluation Questionnaire” and the “Liebowitz Social Anxiety Scale” (Masataka 2019). These findings indicate that CBD oil significantly decreases feelings of social anxiety and may be an effective alternative option for managing anxiety.  

For those who are not familiar with the world of research, the “Gold-Standard” of a designed clinical trial is one that is double-blind, randomized, and crosses-over. 

  • Double-Blind: Neither the researchers nor the participants are unaware of the treatment they are receiving until the end of the study. 
  • Randomized: The treatment (in this case, the order of the treatments) subjects receive is randomly assigned. 
  • Crossover: Participants receive both the experimental (i.e. CBD) and placebo treatments at different time points during the study. 

A study using this approach assessed feelings of anxiety in 24 participants that were diagnosed with various stages of Parkinson’s disease.  Researchers found that a dose of 300 mg of CBD prior to a Simulated Public Speaking Test significantly decreased feelings of anxiety throughout the assessment (de Faria 2020). In concordance with the previous studies, this again suggested the oral administration of CBD oil could help stabilize the autonomic dysregulation that leads to anxiety. However, the three studies we have discussed to this point all involved clinical populations (PTSD, SAD, and Parkinson’s disease), but what about these effects in a relatively healthy adult population? 

A recent study performed in relatively healthy adults that regularly attended a psychiatric clinic looked to further explore the effects of CBD on anxiety. Researchers observed 72 patients over a 3-month period who were administering 25 mg of CBD oil in a capsule in the morning following breakfast (Shannon 2019)

(Why after breakfast you ask? Read here how consuming CBD with a meal can change its absorption and bioavailability!)

Within the first month, nearly 80% of participants reported decreases in measures of anxiety, however, a small portion (15%) of patients did report a worsening in their feelings of anxiety after 1-month. Improvement in feelings of anxiousness persisted throughout the 3-month duration of the study. Leading researchers to conclude that CBD may be beneficial for the treatment of anxiety and anxiety-related disorders, but that more clinical research is needed to validate these effects (Shannon 2019).  

Within the context of the studies reviewed in this article, it appears that CBD oil may hold beneficial effects on feelings of anxiety and anxiety-related disorders. Participants in these studies consumed anywhere from 6-300 mg of CBD oil, usually in the morning to help manage their symptoms, but significant results were observed at lower doses of 6-25 mg of CBD per day.  The big question though is why? Well, that answer is still unclear, as both the mechanisms underlying anxiety and the physiological actions of CBD on the body are still being understood, but some may suggest that a possible reason for this is CBD’s actions on the serotonin receptor (5-HT1A) and other cannabinoid receptors in the brain and the peripheral tissues of the body (Lee 2017). Serotonin is a chemical that is released throughout the body in response to many different stimuli but is largely associated with mood and a sense of satisfaction or well being. Decreased levels of serotonin have even been associated with symptoms of depression (Dell’Osso 2016 & Kraus 2017).  The CBD molecule can mimic the effects of serotonin by binding to the serotonin receptor, thus partially mimicking serotonin’s effects (Lee 2017). Further, the overactivity of neural communication within the brain could result in anxiety as well (Ressler 2011). Within the brain, CBD can act on neural synapses, mimicking the effects of our endogenous cannabinoids, like anandamide, and suppress the frequency of signals that are being sent between neurons, quite literally calming down the brain.  

Summary

There is preliminary scientific evidence that suggests CBD may naturally support our mental welfare, but before turning to CBD as a more natural alternative to managing your stress, make an appointment with your physician to discuss the transition so they can monitor your unique experience using CBD. There is still a lot we don’t know about CBD regarding potential drug interactions and long term effects, so work with your physician to find out what’s best for your unique needs. 

Be well.  

If you feel like you need help with symptoms of anxiety or are having thoughts of suicide please seek help. The National Suicide Prevention Hotline is available 24-hrs a day: 1-800-273-8255

Looking for more 6° Wellness Content? 

Website: www.sixdegreeswellness.com 

Instagram: @6degreeswellness

Podcast: CBD Deep Dive anchor.fm/6degrees 

Disclaimer: Part of our mission is to always present the latest cannabinoid research; however, none of this is intended to represent the safety or efficacy of our products. These statements and our products have not been evaluated by the FDA, and our products are not intended to diagnose, prevent, treat or cure any disease. You should consult your physician or other health care professional before taking CBD to determine if it is right for your needs.

Jonny Lisano, Ph.D

JONNY LISANO, Ph.D.

Jonny received his Ph.D. from the University of Northern Colorado (UNC) in Exercise Physiology.  During his time at (UNC) he and his advisor established the first cannabis and exercise performance laboratory in the nation.  Jonny’s early research pertaining to cannabis focused on the assessment of how the long-term use of cannabis products in physically active individuals affected parameters of overall health and exercise performance.  As he progressed into the field of cannabis research his focused shifted from exercise performance to that of how CBD affects immune function in physically active individuals who are using cannabis products.

Jonny has always been an advocate for living a healthy lifestyle and believes CBD can be an integral part of that.  His focus at 6° Wellness is to provide and explain the most current scientific knowledge pertaining to cannabis in a way everyone can understand, and providing recommendations on how the products we offer can fit into your lifestyle.

In his free time Jonny enjoys training for competitive obstacle course races, hiking the beautiful Colorado backcountry, and partaking in the occasional beer from the local craft beer scene.

References:

Corroon, J., & Phillips, J. A. (2018). A Cross-Sectional Study of Cannabidiol Users. Cannabis and Cannabinoid Research, 3(1), 152–161. https://doi.org/10.1089/can.2018.0006

Dell’Osso, L., Carmassi, C., Mucci, F., Marazziti, D. (2016). Depression, Serotonin and Tryptophan. Curr. Pharm. Des., 22(8): 949-54. 

De Faria, S.M., de Morias Fabricio, D., Tumas, V., Castro, P.C., Ponti, M.A., Hallak, J.E., Zuardi, A.W., Crippa, J.A.S., Chagas, M.H.N. (2020). Effects of acute cannabidiol administration on anxiety and tremors induced by a Simulated Public Speaking Test in patients with Parkinson’s disease. J. Psychopharmacol., 34(2):189-196. 

Kraus, C., Castren, E. Kasper, S., Lanzenberger, R. (2017). Serotonin and neuroplasticity – Links between molecular, functional and structural pathophysiology in depression. Neurosci Biobehav Rev., 77:317-326. 

Lee, J.L.C., Bertoglio, L.J., Guimaraes, F.S., Stevenson, C.W. (2017). Cannabidiol regulation of emotion and emotional memory processing: relevance for treating anxiety-related and substance abuse disorders. Br. J. Pharmacol., 174(19): 3242-3256.

Masataka, N. (2019). Anxiolytic Effects of Repeated Cannabidiol Treatment in Teenagers With Social Anxiety Disorders. Front Psychol., 10:2466. 

Ressler, K.J., (2010). Amygdala Activity, Fear, and Anxiety: Modulation by Stress. 67(12):1117-1119. 

Shannon, S., Opila-Lehman, J. (2016) Effectiveness of Cannabidiol Oil for Pediatric Anxiety and Insomnia as Part of Posttraumatic Stress Disorder: A Case Report. Perm J., 20(4): 16-005.

Shannon, S., Lewis, N., Lee, H., Hughes, S. (2019) Cannabidiol in Anxiety and Sleep: A Large Case Series. Perm J., 23: 18-41. 


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Written By: Dr. Jonny Lisano, Ph.D.

Photo by Gregory Pappas on Unsplash

Sleep: We all need it, but most of us can’t seem to get enough. We’ve all been there, the alarm goes off and you feel like you only fell asleep an hour ago, but could CBD help support natural sleep rhythms? 

Cannabidiol, or CBD, is one of the two major phytocannabinoids found in cannabis along with delta-9-tetrahydrocannabinol, also known as THC. However, unlike THC, CBD does not produce intoxicating effects (which you can read more about here in one of our previous blog posts). There are anecdotal claims across the industry and consumers alike that CBD can help support healthy sleep, but what does the research actually say? 

What is “Normal” Sleep? 

Before we start discussing scientific research on CBD and sleep, we should first discuss the stages of sleep that make up the sleep cycle. There are four general stages of sleep, which can further be divided by the presence of rapid eye movement (REM). These two categories are non-REM, which the first three stages are in, and REM where the fourth and final stage of the sleep cycle occurs.

Non-Rapid Eye Movement 

Non-REM Stage 1 (N1): Light sleep

This stage is the transition between wakefulness and sleep.  In this stage of transition, brain waves known as “theta waves” first make an appearance. During this stage of sleep, you can be easily awoken by sounds or touch.  This is also the stage of sleep where hypnic jerks occur and involuntary muscle contractions can momentarily startle you awake. This stage typically lasts 10-15 minutes per cycle.

Non-REM Stage 2 (N2): Moderate sleep

In the second stage of sleep, theta waves become more prevalent and are joined by two more brain wave complexes. These two new brain waves are known as k-complexes and sleep spindles. It is theorized that k-complexes help with memory consolidation and that sleep spindles aid in filtering out non-threatening sounds and touches to prevent you from being startled awake and disrupting the sleep cycle when your partner is tossing and turning, or when the dog is pacing back and forth across the wooden floor all night. So, while you are not yet in deep sleep it’s much more difficult to wake you up than it would be during N1.   

Non-REM Stage 3 (N3): Deep sleep

This stage of Non-REM sleep is commonly referred to as slow-wave sleep or deep sleep. That is because, during this stage of sleep long, slow delta waves become present and characterize the onset of this sleep stage. In this stage of sleep, it is extremely difficult for your body to be woken-up. If you’ve ever been jolted awake in the middle of the night by a loud sound but your roommate or partner is still sleeping peacefully, it’s most likely because they were in the N3 stage of sleep while you were in one of the lighter stages of sleep (N1, N2, REM). This stage of deep sleep is where your body secretes hormones like growth hormone to aid in tissue repair and recovery throughout your body. This stage of sleep is very critical, especially if you live an active lifestyle because this is where the majority of muscle repair and growth occur. So if you are an active individual, getting adequate deep sleep is essential to your recovery process.  

Rapid Eye Movement

Rapid Eye Movement (REM): “Dreaming” Sleep

This stage is called rapid eye movement (REM) because during this stage a sleeping individual’s eyes will move back and forth rapidly signifying that dreams may be occurring. The deepness of this stage of sleep is not to the extent of that of N2 or N3 and you can be easily awoken.  This stage is often referred to as paradoxical because your brain activity mimics that of being awake but your body is physically inactive.  This is because during this stage of sleep your brain prevents your body from physically acting out your dreams, keeping you and anyone sleeping near you safe. This stage of sleep typically lasts in 15-20 minute intervals.  

While a complete sleep cycle lasting anywhere from 90 to 120-minutes can include all 4 stages, they do not typically occur in sequential order and then start over for the next sleep cycle. You typically progress in the following order: N1, N2, N3, N2, REM and then either go back to N1 or back to N2 starting the cycle over again. We typically have more deep sleep at the beginning of the night, and more REM sleep towards the end of the night. During a “good night’s sleep” you’ll most likely complete anywhere between 4-5 complete cycles. Also, waking up at the completion of a cycle will lead you to feel more rested than if you are awoken in the middle of a cycle. However, as most of us know this is not always the case. Factors like stress, anxiety, pets, and kids are but just a few factors that can disrupt our sleep habits. You can see below in Figure 1 the difference in the sleep cycle progression during a good night’s sleep and a bad night’s sleep. Panel A of Figure 1 depicts a “good night’s sleep” with no times of awakeness during the night and the majority of time spent in the light (N1, N2), deep (N3) and REM stages of sleep. To the right in panel B of Figure 1, you can see an example of a “bad night’s sleep”, and the interruptions of periodically waking up throughout the night, disrupting the natural sleep stage rhythm.  

Sleep data was collected from a 33-year-old female on seperate nights

Research on CBD and Sleep

Questions around CBD and sleep have been gaining in popularity, begging the question “Could CBD help support natural sleep habits, leading to a more restful night’s sleep?” Let’s see what we currently know from the research. 

It is well established that anxiety can elicit changes in the sleep cycle and disrupt natural sleep habits.  A study from 2012 using a rat-model of anxiety found that the injection of CBD into the central nucleus of the amygdala (yes, that means they injected CBD directly into a specific area of the rat’s brain), known as the “fear center” of the brain, blocking the anxiety-induced suppression of REM sleep. In other words, CBD helped increase the duration of REM sleep in rats suffering from anxiety (Hsiao 2012).  Yet, there was no significant effect of CBD on overall sleep duration. The implications of this study are hard to determine, however, as it was done in an animal study, and CBD was injected directly into the brain, which makes it difficult to determine whether there are any real-world implications of this.  So, what about some other studies that don’t involve brain injections?

Another study published in 2013 assessed sleep duration in rats receiving either 2.5, 10 or 40 mg of CBD per kilogram of body weight. However, keep in mind that due to pharmacokinetics of mammals a 2.5 mg/kg dose of CBD in a rat is not equivalent to 2.5 mg/kg in a human. Instead, the human equivalent doses of 2.5, 10 and 40 mg/kg in rats would be more comparable to doses of 0.20, 0.81 and 3.25 mg/kg respectively. In a 150 lb adult, this would equate to taking doses of ~14, 55, or 220 mg, which are reasonable doses for a human.  Interestingly enough, there was no difference in sleep duration in animals receiving the lowest dose of CBD compared to the control group; however, in both of the higher CBD dose groups, there was a significant increase in overall sleep time, suggesting that taking a human equivalent dose of ~55 mg of CBD prior to bedtime could increase sleep duration (Chagas 2013). Yet, as interesting as the results of this study are, like the first study, it was still performed in an animal model and despite the promising results is still not directly applicable to humans.  

A case study of an adolescent suffering from post-traumatic stress disorder (PTSD), a severe form of anxiety, found that the administration of 25 mg of CBD prior to bedtime decreased the patient’s sleep scale score from an initial score of 59 to a final score of 38 on the Sleep Disturbance Scale for Children (a score above 50 indicates sleep disorder on this scale). It was also noted that by the end of the case study that the child was sleeping in her own room most nights and reported no side effects from their CBD use (Shannon 2016), but what about the effects of CBD on sleep in adults? 

Remember how we learned that when your body enters REM sleep that our body secretes chemicals to keep us from acting out our dreams? Well, there is also a condition called REM behavior disorder (RBD). Individuals suffering from RBD do not secrete the proper chemicals to keep their body from acting out their dreams, and can often cause them to act out vivid or unpleasant dreams through shouts and violent arm and leg movements.  Researchers on a study from 2014, assessed if the administration of CBD in individuals suffering from RBD had any changes in their symptoms resulting from this condition. The four participants received anywhere from 75-300 mg of CBD prior to bedtime and saw a significant decrease in the number of RBD related events, and again similar to the previous study did not report any serious side effects (Chagas 2014).  

Further, in a relatively healthy population, a study assessed the sleep quality of 25 patients from a psychiatric clinic over the course of a 3-month period using the Pittsburg Sleep Quality Index (PSQI). They found that the administration of CBD right after dinner improved sleep quality from initial assessment to the one-month reassessment, and remained lower compared to baseline till the end of the study at 3-months.  Most subjects (>90%) self-administered 25 mg of CBD following their dinner, but some subjects reported using as much as 75 mg (Shannon 2019). The range in doses administered to participants in this study could be due to multiple factors including participant body weight. As we discussed in a previous article, the reason that participants consumed their CBD with a meal is that it can increase CBD’s absorption and bioavailability, which you can read here. Of the 5 studies we have discussed thus far, this is probably the most applicable to those seeking to use CBD products to support natural sleep rhythms.  

It is important to note, as we wrap things up for this post, that not all cannabinoids are created equal with respect to sleep. In our role as researchers, we often get asked about cannabinoids for sleep, but THC and CBD have vastly different effects on our sleep architecture. For example, THC has been shown to decrease the time it takes individuals to fall asleep (Tringale 2011), but these subjects also experienced a lower quality of sleep (Ogeil 2015), less time in moderate to deep sleep (Nicholson 2004) and experienced overall less time sleeping (Gorelick 2013), which over the long term can have detrimental effects on our sleep habits. In a different study aimed at understanding user preferences when using cannabis for sleep,  some adult participants reported that they preferred a cannabis product with higher CBD and lower THC (Belendiuk 2015) over the long term. At the time of writing this article, there have been no known detrimental effects of using only CBD for maintaining healthy sleep architecture.

While the current research shows promising effects for the use of products containing CBD to promote natural sleep habits, more research is still needed to identify the underlying physiological mechanisms, as well as the direct effects on the four stages of sleep we discussed at the start of this article.  

Looking for more 6° Wellness Content? 

Website: www.sixdegreeswellness.com 

Instagram: @6degreeswellness

Podcast: CBD Deep Dive anchor.fm/6degrees 

Disclaimer: Part of our mission is to always present the latest cannabinoid research; however, none of this is intended to represent the safety or efficacy of our products. These statements and our products have not been evaluated by the FDA, and our products are not intended to diagnose, prevent, treat or cure any disease. You should consult your physician or other health care professional before taking CBD to determine if it is right for your needs.

Jonny Lisano, Ph.D

JONNY LISANO, Ph.D.

Jonny received his Ph.D. from the University of Northern Colorado (UNC) in Exercise Physiology.  During his time at (UNC) he and his advisor established the first cannabis and exercise performance laboratory in the nation.  Jonny’s early research pertaining to cannabis focused on the assessment of how the long-term use of cannabis products in physically active individuals affected parameters of overall health and exercise performance.  As he progressed into the field of cannabis research his focused shifted from exercise performance to that of how CBD affects immune function in physically active individuals who are using cannabis products.

Jonny has always been an advocate for living a healthy lifestyle and believes CBD can be an integral part of that.  His focus at 6° Wellness is to provide and explain the most current scientific knowledge pertaining to cannabis in a way everyone can understand, and providing recommendations on how the products we offer can fit into your lifestyle.

In his free time Jonny enjoys training for competitive obstacle course races, hiking the beautiful Colorado backcountry, and partaking in the occasional beer from the local craft beer scene.

References:

Belendiuk, K.A., Babson, K.A., Vrandey, R., Bonn-Miller, M.O. (2015) Cannabis species and cannabinoid concentration preference among sleep-disturbed medicinal cannabis users. Addict Behav. 50: 178-81. 

Chagas, M.H., Crippa, J.A., Zuardi, A.W., Hallak, J.E., Machado-de-Sousa, J.P., Hirotsu, C., Maia, L., Andersen, M.L. (2012) Effects of acute systemic administration of cannabidiol on sleep-wake cycle in rats. J. Psychopharmacol, 27(3):312-6. 

Chagas, M.H., Eckeli, A.L., Zuardi, A.W., Pena-Pereira, M.A., Sobreira-Neto, M.A., Sobreira, E.T., Camilo, M.R., Bergamaschi, M.M., Schenck, C.H., Hallak, Tumas, V., Crippa, J.A. (2014) Cannabidiol can improve complex sleep-related behaviors associated with rapid eye movement sleep behavior disorder in Parkinson’s disease patients: a case series. J Clin Pharm Ther., 39(5): 564-566. 

Gorelick, D.A., Goodwin, R.S., Schwilke, E., Schroeder, J.R., Schwope, D.M., Kelly, D.L., Ortemann-Renon, C., Bonnet, D., Huestis, M.A. (2013) Around-the-clock oral THC effects on sleep in male chronic daily cannabis smokers. Am J Addict., 22(5): 510-514. 

Hsiao, Y.T., Yi, P.L., Li, C.L., Chang, F.C. (2012) Effect of cannabidiol on sleep disruption induced by the repeated combination tests consisting of open field and elevated plus-maze in rats. Neuropharmacology, 62(1): 373-84. 

Nicholson, A.N., Turner, C., Stone, B.M., Robson, P.J. (2004) Effect of Delta-9-tetrahydrocannabinol and cannabidiol on nocturnal sleep and early-morning behavior in young adults. J. Clin. Psychopharmacol, 24(3): 305-13. 

Ogeil, R.P., Phillips, J.G., Rajaratnam, S.M., Broadbear, J.H. (2015) Risky drug use and effects on sleep quality and daytime sleepiness. Hum. Psychopharmacol, 30(5): 356-63. 

Shannon, S., Opila-Lehman, J. (2016) Effectiveness of Cannabidiol Oil for Pediatric Anxiety and Insomnia as Part of Posttraumatic Stress Disorder: A Case Report. Perm J, 20(4): 16-005.

Shannon, S., Lewis, N., Lee, H., Hughes, S. (2019) Cannabidiol in Anxiety and Sleep: A Large Case Series. Perm J., 23: 18-41. 

Tringale, R., Jensen, C. (2011) Cannabis and Insomnia. O’Shaughnessy’s, 31-32. 


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Disclaimer: Part of our mission is to always present the latest cannabinoid research; however, none of this is intended to represent the safety or efficacy of our products. These statements and our products have not been evaluated by the FDA, and our products are not intended to diagnose, prevent, treat or cure any disease. You should consult your physician or other health care professional before taking CBD to determine if it is right for your needs.

Currently, there are athletes across the country advocating for the use of products containing CBD following their workouts to help them recover.  Is there any merit to this from a physiological, science-based perspective? 

Written by: Dr. Jonny Lisano, Ph.D.

Exercise and Muscle Soreness

Regardless if you are an elite athlete, fitness fiend or a weekend warrior, odds are that you have experienced localized muscle soreness and swelling in the days following your workouts.  This pain and swelling typically become apparent 24-48 hours following your workout and can last for days (Lewis et al., 2012). This swelling and pain might even have led you to miss a workout or two. This is commonly referred to within the fitness community as DOMS (delayed onset muscle soreness) (Lewis et al., 2012). It’s a common misconception that DOMS is the result of lactic acid accumulation during your workout. While lactic acid is produced in large quantities during intense exercise to help provide quick energy to exercising muscles, it is not the primary perpetrator for your exercise-related muscle soreness. Lactic acid quickly dissociates into lactate and hydrogen (H+). While the lactate is harmless and is transported to the blood and processed quickly by other tissues like the liver, the hydrogen ion can act as a free radical and cause chemical damage to the muscle if not adequately dealt with (Bailey et al., 2004)

Inflammation

The root cause of DOMS is actually the chemical and physical damage to muscle as a result form exercise. Yes, you read that right, when you exercise you cause damage to your muscles (that’s ok because this is actually how your body gets stronger, which we’ll discuss later).  This damage causes the inner contents of cells to be released, which are not normally found outside of the cell. These inner contents along with locally secreted factors known as cytokines and chemokines act as a chemical signal to immune cells, primarily monocytes, circulating in the blood (Peake et al., 2017). These immune cells then follow that combined chemical signal to the site of damage and migrate into those local tissues. It is during this process that some of the monocytes become what are known as M1 macrophages. What M1 macrophages do is they “eat” up and clear any of the damaged cellular debris while simultaneously secreting factors to help recruit more immune cells to the area and make the area more permeable to fluid, which promotes circulation of fluid to bring in nutrients and more immune cells, but also flush out debris and release the immune cell factors that promote migration to the area (Ley 2017)

Now, this is a good, natural process and is needed to clear out the damaged tissue before new tissue growth and repair can be stimulated by M2 macrophages. The M2 macrophages are responsible for stimulating muscle satellite cells “baby muscle cells” to grow and mature (Ley 2017). This not only helps to replace damaged tissue but also, in theory, makes the muscle tissue stronger than it was previously so it can handle more stress for the next bout of exercise. This whole process normally takes a few days from start to finish, with the inflammation and pain subsiding within a couple of days. This is what is known as “acute” inflammation. Acute inflammation is a good thing, it naturally helps promote muscle repair and recovery.  

However, when the inflammation stimulated by exercise-related muscle damage persists for more than a few days it becomes what is known as “chronic” inflammation. Chronic inflammation is not desirable and can result in not only the breakdown and removal of damaged tissue but normal, healthy tissue as well (Dalle et al. 2017).  This issue of chronic-inflammation is actually commonly seen in athletes and is one aspect of what is known as overtraining syndrome. One of the ways overtraining syndrome can be induced is through excessive intense exercise, which we already know can cause acute inflammation. With inadequate time for recovery, this is where acute inflammation turns into chronic inflammation. This ultimately results in loss of muscle mass and strength called sarcopenia. So, how do we manage the balance between acute and chronic inflammation to maximize recovery? 

Well, one common method is through the use of non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen.  These drugs help limit the pro-inflammatory process and can help reduce exercise-related pain. However, when taken chronically or in excessive amounts, NSAIDs can cause damage to organs, like your kidneys (Whelton et al., 1991). Could cannabidiol (CBD) potentially be a natural way to help mitigate excessive inflammation resulting from exercise? 

Cannabidiol (CBD)

As you may know, CBD is one of more than 100+ cannabinoids present in the hemp plant (Cannabis Sativa L.). It exerts its physiological effects by acting on the body’s endocannabinoid system. Receptors like CB1, CB2, and GPR55 are all cannabinoid receptors present in immune tissues and cells. Like monocytes, they have been scientifically observed to have varying interactions with CBD.  

Cannabidiol (CBD) and Inflammation

Surprisingly, there is extremely limited research on how both the acute and chronic use of CBD affect the post-exercise inflammatory process in humans. The most promising research with respect to this area has been performed using cell cultures (i.e. performing experiments on cells that are grown outside of the body in highly sterile, highly controlled conditions.)

As mentioned earlier, cytokines released by immune cells and other local tissues, such as muscle, act as a chemical signal that can either promote or suppress the inflammatory process. When a cytokine promotes inflammation, it is referred to as pro-inflammatory, and when it suppresses inflammation it is classified as anti-inflammatory. Remember we stated earlier that a little bit of inflammation is a good thing, and low levels of pro-inflammatory cytokines, such as interleukin-6 (IL-6), are actually necessary for muscle growth and repair (Kurosaka et al., 2013).  Too much of it, however, can be detrimental (Kurosaka et al.,  2013)

One study, assessing the effects of the pre-treating immune cells with either CBD or delta-9-tetrahydrocannabinol (THC) prior to an immune challenge (which could represent a cold or an intense exercise bout) resulted in the suppression of the immune cell’s release of proinflammatory cytokines, like IL-6 and tumor necrosis factor-alpha (TNFα). Further, it was found that as the dose of these cannabinoids was increased, there was a greater immunosuppressive effect on these cytokines. More interestingly, CBD provided a greater immunosuppressive effect than THC at the same concentrations (Kozela et al. 2010). Meaning that CBD on its own has greater immunosuppressive effects than THC on its own, and could potentially prevent the excessive release of IL-6, which can lead to chronic inflammation.  

In a human study comparing the circulating concentrations of interleukin-17 (IL-17), another pro-inflammatory cytokine, between chronic cannabis users and non-users that were either healthy or had multiple sclerosis (MS), showed that both cannabis user groups (healthy and MS) had significantly lower circulating concentrations of the pro-inflammatory IL-17 cytokine (Sexton et al. 2014). The cytokine IL-17 acts on other immune cells, stimulating them to release chemokines that attract more immune cells like monocytes to the tissue. Keep in mind that this study was not exclusive to CBD and participants were using products that contained both THC and CBD.  

However, while these results are promising for the scientifically observed anti-inflammatory effects of CBD, there is still limited/no evidence of the effects of CBD on exercise-induced inflammation in humans. What is even more interesting, is that recent research published in November 2019 showed that chronic exercise can significantly change the expression of CB1 and CB2 receptors in various types of immune cells. Thus, chronic exercise could change the way your immune cells respond to cannabinoids like CBD (Valencia-Sanchez et al., 2019). Increasing the number of CB1 or CB2 receptors expressed on immune cells would, in theory, make your cells more responsive to cannabinoids like CBD, meaning the anti-inflammatory effects could become more pronounced. On the opposite end of that spectrum, if exercise decreases the number of CB1 or CB2 receptors expressed by immune cells this could limit the anti-inflammatory effects of cannabinoids.  

Yet, this begs the question of are there individuals that are using cannabis products like CBD to help with exercise pain and inflammation? In a survey study that I published during my Ph.D., we asked physically active cannabis users, why they were using cannabis products either before, during or after their exercise. Pain mitigation and recovery were two of the most common reasons for use. With cannabis being used for pain at all three time-points (before, during and after exercise), whereas recovery was only reported after exercise (Lisano et al. 2019). However, it was unclear if the pain they were using cannabis to mitigate was exercise-induced pain or a pre-existing condition like arthritis. More research will be needed to provide a definitive answer on if taking CBD following exercise can help reduce localized inflammation, swelling, and pain associated with exercise. Exercise in itself has anti-inflammatory effects, and it is still unclear if the anti-inflammatory effects of CBD would combine with the anti-inflammatory effects of exercise leading to a greater combined immunosuppressive effect. 

Final Thoughts

Exercise-induced inflammation is a complex process, of which we have only just scratched the surface in this article. You now know that the DOMS experienced following exercise is the result of exercise-related damage to the muscles, which results in localized inflammation (swelling) of the tissue that can result in pain. Cannabinoids, especially CBD, have been observed to have anti-inflammatory effects, which may indicate that the use of CBD following exercise can help mitigate the exercise-associated inflammation and get you back to your workouts in the following days feeling great. More research on this to come. 

Looking for more 6° Wellness Content? 

Website: www.sixdegreeswellness.com 

Instagram: @6degreeswellness

Podcast: CBD Deep Dive anchor.fm/6degrees

Jonny Lisano, Ph.D

JONNY LISANO, Ph.D.

Jonny received his Ph.D. from the University of Northern Colorado (UNC) in Exercise Physiology.  During his time at (UNC) he and his advisor established the first cannabis and exercise performance laboratory in the nation.  Jonny’s early research pertaining to cannabis focused on the assessment of how the long-term use of cannabis products in physically active individuals affected parameters of overall health and exercise performance.  As he progressed into the field of cannabis research his focused shifted from exercise performance to that of how CBD affects immune function in physically active individuals who are using cannabis products.

Jonny has always been an advocate for living a healthy lifestyle and believes CBD can be an integral part of that.  His focus at 6° Wellness is to provide and explain the most current scientific knowledge pertaining to cannabis in a way everyone can understand, and providing recommendations on how the products we offer can fit into your lifestyle.

In his free time Jonny enjoys training for competitive obstacle course races, hiking the beautiful Colorado backcountry, and partaking in the occasional beer from the local craft beer scene.

References:

Bailey, D.M., Young, I.S., McEneny, J., Lawrenson, L., Kim, J., Barden, J., Richardson, R.S. 2004. Regulation of Free Radical Outflow From an Isolated Muscle Bed in Exercising Humans. Am. J. Physiol. Heart Circ. Physiol., 287(4):H1689-99. 

Dalle, S. Rossmeislova, L., Koppo, K. 2017. The Role of Inflammation in Age-Related Sarcopenia. Front. Physiol., 8: 1045. 

Kozela, E., Pietr, M., Juknat, A., Rimmerman, N., Levy, R., Vogel, Z. 2010. Cannabinoids Delta(9)-tetrahydrocannabinol and Cannabidiol Differentially Inhibit the Lipopolysaccharide-Activated NF-kappaB and interferon-beta/STAT Proinflammatory Pathways in BV-2 Microglial Cells. J. Biol. Chem., 285(3): 1616-26. 

Kurosaka, M., Machida, S., 2013. Interleukin-6-induced Satellite Cell Proliferation Is Regulated by Induction of the JAK2/STAT3 Signalling Pathway Through Cyclin D1 Targeting. Cell Prolif., 46(4): 365-73.

Lewis, P.B., Ruby, D., Bush-Joseph, C.A. 2012. Muscle Soreness and Delayed-Onset Muscle Soreness. Clin Sports Med., 31(2):255-62. 

Ley, K. 2017. M1 Means Kill; M2 Means Heal. J. Immunol., 199(7):2191-2193.

Lisano, J.K., Phillips, K.T., Smith, J.D., Barnes, M.J., Stewart, L.K. 2019. Patterns and Perceptions of Cannabis Use with Physical Activity. Cannabis, 2(2):151-64.

Peake, J.M., Roberts, L.A., Figueiredo, V.C., Egner, I., Krog, S., Aas, S.N., Suzuki, K., Markworth, J.F., Coombes, J.S., Cameron-Smith, D., Raastad, T. 2017. The Effects of Cold Water Immersion and Active Recovery on Inflammation and Cell Stress Responses in Human Skeletal Muscle After Resistance Exercise. J. Physiol., 595(3):695-711. 

Sexton, M., Cudaback, E., Abdullah, R.A., Finnel, J., Mischley, L.K., Rozga, M., Lichtman, A.H., Stella, N. 2014. Cannabis Use by Individuals with Multiple Sclerosis: Effects on Specific Immune Parameters.  Inflammopharmacology, 22(5): 295-303. 

Valencia-Sanchez, S., Nava-Castro, K.E., Palacios-Arreola, M.I., Prospero-Garcia, O., Morales-Montor, J., Drucker-Colin, R. 2019. Chronic exercise modulates the cellular immunity and its cannabinoid receptors expression. PloS One, 14(11): e0220542. 

Whelton, A., Hamilton, C.W., 1991. Nonsteroidal Anti-Inflammatory Drugs: Effects on Kidney Function. J. Clin. Pharmacol., 31(7): 588-98. 


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Disclaimer: Part of our mission is to always present the latest cannabinoid research; however, none of this is intended to represent the safety or efficacy of our products. These statements and our products have not been evaluated by the FDA, and our products are not intended to diagnose, prevent, treat or cure any disease. You should consult your physician or other health care professional before taking CBD to determine if it is right for your needs.

Written by: Dr. Jonny Lisano, Ph.D. 

When it comes to cannabinoids from the cannabis plant, in particular, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), we often hear terms like “psychoactive” or “non-psychoactive” associated with these compounds. The compound THC is commonly regarded as psychoactive and CBD non-psychoactive. Yet, how do we actually define psychoactive effects, and are those terms being used correctly? Let’s take a closer look…

Defining Psychoactive 

First, let’s discuss what psychoactive really means.  A psychoactive substance is any chemical that produces mind-altering effects like changes in mood, perception, cognition, or behavior.  Typically, when we think of psychoactive drugs we think of stimulants like amphetamines (Adderall), depressants (alcohol), narcotics (opioids) or hallucinogens (LSD). When it comes to cannabinoids, we typically say THC is psychoactive and CBD is non-psychoactive.  Meaning CBD doesn’t produce any alterations in mood, perception, cognition, or behavior. 

This belief is largely based on the fact that CB1 cannabinoid receptors of the endocannabinoid system are heavily expressed within the central nervous system. THC can bind and activate the CB1 receptor and cause psychoactive effects; however, while CBD can bind the CB1 receptor it can not activate it or cause the associated psychoactive effects. Thus, the mantra “THC is psychoactive but CBD isn’t”. 

What if I told you that technically that’s not correct, and CBD is indeed psychoactive? Now hold on… don’t get too excited, CBD is not going to produce the same psychoactive effects as THC, but it certainly can induce alterations in your mental state. Specifically, alterations in your mood. The endocannabinoid system is much more complex than was initially thought and includes more than just the CB1 receptor that THC acts on. There are other cannabinoid receptors within the central nervous system that can cause mood alterations in response to CBD. 

Defining a Mood

Now, the definition of a mood is a temporary state of mind or feeling.  One of the most common anecdotal reasons individuals use CBD products, like CBD oil, is to help dampen their feelings of anxiety.  Anxiety is simply defined as a feeling of worry, nervousness or unease. That definitely fits the definition of a mood, as typically we feel very anxious prior to some major event like public speaking, meeting an online date for the first time, holidays with the in-laws, or interviewing for that job we really want.  

CBD and Mood (Anxiety)

But what does science say about CBD and anxiety? Well for starters, in a double-blind randomized clinical trial in individuals that have opioid use disorder withdrawing from use, it was found that individuals who received CBD had reduced craving and anxiety in addition to lower salivary cortisol (our stress hormone) concentrations compared to placebo (Hurd et al. 2019).  In another study, 8-weeks of CBD administration to individuals suffering from PTSD, which is classified as an anxiety disorder, 91% of individuals experienced a reduction in PTSD related symptoms while also receiving regular psychiatric care (Elms et al. 2019).  Finally, in 18 to 19 year-old teenagers it was found that taking 300mg of CBD daily for 4-weeks significantly decreased their scores on two separate measures of social anxiety disorder compared to a control group (Masataka 2019).  So, that is three recent studies that demonstrate CBD could be beneficial in individuals suffering from anxiety disorders. Feelings of anxiety result from underlying psychological and neurochemical imbalances. As such, CBD technically is psychoactive because in order to reduce feelings of anxiety it would have to be causing effects at the neurochemical and psychological level.  The mechanisms of which are still to be understood. 

A More Accurate Classification

I know, now you’re probably thinking, “Well if CBD is psychoactive what terminology should we use instead?”. That’s a great question! We believe that instead of using psychoactive and non-psychoactive to differentiate the effects of specific cannabinoids like THC and CBD we should start using intoxicating and non-intoxicating. An intoxicating substance is something that causes an individual to temporarily lose control of their faculties (i.e. hearing, speaking, seeing, balance, thoughts, understanding etc.).  Alcohol, opioids, and THC are all intoxicating substances, but CBD is not, it doesn’t have the intoxicating side effects of THC. CBD does not impair cognition in adults (Colizzi & Bhattacharyya 2017, Martin et al. 2019), and has actually been shown to counteract the cognitive deficits associated with long term THC use (Solowij, 2018). 

Final thoughts

By definition and based off observed effects, CBD is indeed psychoactive, which is by no means a bad thing. However, to better differentiate CBD from other psychoactive substances like THC and opioids we should stop referring to CBD as non-psychoactive but rather non-intoxicating, as CBD does not alter our cognitive faculties the way other compounds do. 

Looking for more 6° Wellness Content? 

Website: www.sixdegreeswellness.com 

Instagram: @6degreeswellness

Podcast: CBD Deep Dive anchor.fm/6degrees 

Jonny Lisano, Ph.D

JONNY LISANO, Ph.D.

Jonny received his Ph.D. from the University of Northern Colorado (UNC) in Exercise Physiology.  During his time at (UNC) he and his advisor established the first cannabis and exercise performance laboratory in the nation.  Jonny’s early research pertaining to cannabis focused on the assessment of how the long-term use of cannabis products in physically active individuals affected parameters of overall health and exercise performance.  As he progressed into the field of cannabis research his focused shifted from exercise performance to that of how CBD affects immune function in physically active individuals who are using cannabis products.

Jonny has always been an advocate for living a healthy lifestyle and believes CBD can be an integral part of that.  His focus at 6° Wellness is to provide and explain the most current scientific knowledge pertaining to cannabis in a way everyone can understand, and providing recommendations on how the products we offer can fit into your lifestyle.

In his free time Jonny enjoys training for competitive obstacle course races, hiking the beautiful Colorado backcountry, and partaking in the occasional beer from the local craft beer scene.


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Disclaimer: Part of our mission is to always present the latest cannabinoid research; however, none of this is intended to represent the safety or efficacy of our products. These statements and our products have not been evaluated by the FDA, and our products are not intended to diagnose, prevent, treat or cure any disease. You should consult your physician or other health care professional before taking CBD to determine if it is right for your needs.

Photo Credit: Nathan Eigenfeld

What factors should you consider when deciding how much CBD you should be taking? 

Written by: Dr. Jonny Lisano, Ph.D.

        You’ve heard all about the benefits of cannabidiol (CBD) and you are wanting to try it for yourself but you aren’t sure what dosage of CBD you should take. Does this sound like your experience with CBD products? The number one question we are asked at 6° Wellness is, “How much CBD should I be taking?” There are a number of ways to find out what CBD dose is right for you, keeping in mind that research in this growing area is limited. 

        When deciding how much CBD you should be taking, there are multiple factors you should be taking into account. These include age, gender, body size, specific symptoms, and desired effects.  As alluded to earlier, due to limited ongoing research, there is no set dosage of CBD combining the above factors. This is where you get to be what we call a “Citizen Scientist”! Only time, trial and error can determine what the optimal dose of CBD is right for you. 

        Currently, for first-time users and experienced CBD users alike looking to use CBD oil in the form of tinctures, vape or gummies we recommend starting at a lower dose of 5-10 mg of CBD. Then gradually increase your dose in a stepwise manner until you consistently achieve your desired effects. Sticking with one dose for a few days at a time is key. Be patient and give it time.

        Even if you’re taking CBD to mediate some of the negative side-effects of exercise like muscle soreness and inflammation; you might find that you need more CBD following a leg workout than a yoga session to support your post-exercise recovery. You may even discover that you need to take more CBD following a workout than your friend who completed the same workout right along-side you. The amount you need to take may even change over time. 

        Your body is a consistently changing system. This means that you may find that you need to either increase or decrease your CBD dosage to produce your desired effects as time goes on. In this aspect, everyone falls on a continuum. You may discover that you need to take less CBD as you get further into your marathon training regimen, or that you need more CBD to help support joint pain relief as you get older.

        Gender may even play a role in the amount of CBD an individual should consume. As time goes on you may even discover that you might be experiencing previously unthought-of effects, like the support of your mental well-being or your joints feel better in the mornings and evenings. 

        We suggest keeping a record of how much CBD you used when you used it, what you used it for and when/how that dosage made you feel in the hours following.  This can serve you as a quick reference guide for yourself in the future just in case you ever forget! 

        We know, this may sound daunting but rest easy, 6° Wellness always has your needs in mind and hopes to make your experience with CBD as knowledgeable, enjoyable and beneficial as possible! 

        6° Wellness strives to provide you with clear, concise information for CBD dosing.  We achieve this by providing only science-based research. We will continue to provide you with the most reliable and safe information possible on how you can incorporate CBD products into your daily life.

Looking for more 6° Wellness Content? 

Website: www.sixdegreeswellness.com 

Instagram: @6degreeswellness

Podcast: CBD Deep Dive anchor.fm/6degrees 

Jonny Lisano, Ph.D

JONNY LISANO, Ph.D.

Jonny received his Ph.D. from the University of Northern Colorado (UNC) in Exercise Physiology.  During his time at (UNC) he and his advisor established the first cannabis and exercise performance laboratory in the nation.  Jonny’s early research pertaining to cannabis focused on the assessment of how the long-term use of cannabis products in physically active individuals affected parameters of overall health and exercise performance.  As he progressed into the field of cannabis research his focused shifted from exercise performance to that of how CBD affects immune function in physically active individuals who are using cannabis products.

Jonny has always been an advocate for living a healthy lifestyle and believes CBD can be an integral part of that.  His focus at 6° Wellness is to provide and explain the most current scientific knowledge pertaining to cannabis in a way everyone can understand, and providing recommendations on how the products we offer can fit into your lifestyle.

In his free time Jonny enjoys training for competitive obstacle course races, hiking the beautiful Colorado backcountry, and partaking in the occasional beer from the local craft beer scene.


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Disclaimer: Part of our mission is to always present the latest cannabinoid research; however, none of this is intended to represent the safety or efficacy of our products. These statements and our products have not been evaluated by the FDA, and our products are not intended to diagnose, prevent, treat or cure any disease. You should consult your physician or other health care professional before taking CBD to determine if it is right for your needs.

Photo by Louis Reed on Unsplash

New Research on CBD and The Liver 

New research claims that the use of cannabidiol (CBD) can damage the liver, and could have adverse side-effects when used with the over the counter drug acetaminophen. Are these claims warranted and what are the results from these studies really saying? Our Director or Research and Education Dr. Jonny Lisano breaks down the science behind it. 

Written by: Dr. Jonny Lisano, Ph.D. 

Recently, concern has arisen within the CBD industry and consumers alike over the findings from two research studies recently published in the journal Molecules. These studies were performed by a lab cohort from the University of Arkansas for Medical Sciences. The primary aim of these studies was to assess the potential liver toxicity of CBD-rich cannabis extract in mice and assess if there are any negative interactions with the common over-the-counter drug acetaminophen, better known as Tylenol. In this article, we will break down the results of each of these studies, discuss their implications, how they pertain to you, as well as teach you some general concepts when interpreting research studies such as these.

Are High Doses of CBD Toxic to the Liver?

The first study, “Hepatotoxicity of a Cannabinoid-Rich Cannabis Extract in the Mouse Model” was published in April of 2019 (Ewing et al. 2019a). The primary goal of this study was to determine if a single, large dose of CBD or high, daily doses administered for 10-days caused liver damage in mice. There were two primary reasons that this study arose. The first being recent findings from the Università della Campania in Italy which found that doses of CBD induced DNA damage in two human-derived cell lines (don’t worry, we will be discussing that study in a future blog post). Secondly, given the widespread availability of CBD as a food additive and new dietary ingredient, it is imperative to determine what level of consumption could lead to toxic effects. 

So, how much CBD can be consumed before it becomes toxic to the body? In this study, a single, large dose of CBD was administered at doses of 246 mg/kg, 738 mg/kg and 2460 mg/kg to three separate groups of mice. In layman’s terms, they administered 246, 738, and 2460 mg of CBD for every kilogram of the animal’s body weight. I know, your first thought is “Holy cow! That is a ton of CBD!”, but there is something that we first need to discuss before we proceed any further with the results of this study, and that is the concept of human and mouse equivalent doses in research, or “allometric scaling” to take into account the vastly different metabolisms between humans and mice. 

Dosing: Why use an animal model, and why are these doses so high? 

For ethical reasons (sorry, mice!), toxicity studies like these can’t be performed in humans due to the unknown side-effects and the possible lethal effects of the previously un-researched compounds being tested. While it might seem intuitive to base the dose of a drug solely on body weight, and to keep this dose consistent across species, there are large differences in metabolism between species (human vs. mouse), and these must be accounted for when comparing doses. The surface area of the animal/human needs to be taken into account when discussing pharmacokinetics, or the movement of compounds throughout the body. This is because the size of a body can greatly affect the body’s ability to respond to a drug. If toxic effects of a drug are observed in animals, a “conversion factor” must be used to determine at what dose these effects would present themselves in humans. In converting doses between mice and humans a factor of 12.3 is used. For example, consider a compound was administered to a mouse at a dose of 12.3 mg/kg. The human equivalent dose would be 1 mg/kg. Conversely, as it is in this article, if a compound was administered at 2 mg/kg in humans the mouse equivalent dose would be 24.6 mg/kg (2 x 12.3).

Now that you better understand the concept of human and mouse equivalent dosing let’s look back at the doses administered to the mice in this study. Mouse doses of 246, 738 and 2460 mg/kg would equal doses of 20, 60 and 200 mg/kg respectively. For ease of interpretation, we will only use the human equivalent doses (HED) for the remainder of this article (i.e 20, 60 and 200 mg/kg) unless otherwise specified. If we were to administer even the lowest dose of 20 mg/kg to a 150 lb human that would equate to roughly 1,364 mg of CBD, or more than two full 600mg, 2oz bottles of 6° Wellness full-spectrum oil. Now I’m sure you’re thinking to yourself, ”What are these doses based on?”. That’s a great question. The 20 mg/kg dose is based on two clinical trials for the drug EPIDIOLEX, the first FDA approved plant-derived CBD medicine used for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome (two forms of severe childhood epilepsy). The other doses of 60 and 200 mg/kg were based off 3x and 10x the highest recommended dose to truly test if CBD would elicit toxic effects at even the highest limit of consumption. As a side note, it would take almost 23 bottles of our 600 mg full spectrum oil to reach the 200 mg/kg dose in a 150 lb adult (which would be toxic)… Wowza! 

An easy to understand quick conversion table that shows what the equivalant CBD doses are in animals vs. humans at all three experimental doses can be found in Table 1. This table also shows what the relative CBD dose would be in humans of various body weights. 

Table 1: Animal to Human Dose Conversion Table

So, what were the results of this first study?

Getting into the nitty-gritty of this first study. After a large dose of CBD extract researchers observed lethargy (sluggishness) lasting 4-5 hours in the 60 mg/kg HED group and up to 24-hours in the 200 mg/kg HED group. However, there were no observable behavioral differences in the 20 mg/kg HED group. The 60 mg/kg HED group did experience swelling of their livers, but in the 20 or 200 mg/kg HED groups there was no observable liver inflammation. Further, researchers observed a significant increase in liver glutathione, a byproduct of oxidative stress, in the 200 mg/kg HED group but not in the other two groups. This indicates that at this dose of CBD there was increased oxidative stress on the liver, which could potentially lead to liver damage. This study also assessed five blood markers to indicate if liver damage was present. Those markers were ALT, AST, ALP, GGT, and total Bilirubin. While none of these markers were elevated in the 20 mg/kg HED group (indicating no liver damage at this dose) both ALT and AST were elevated in the 60 and 200 mg/kg HED group, and total Bilirubin was elevated in the 200 mg/kg HED group. This implies that the two higher doses of CBD tested in this study did result in liver damage. 

In the second part of this study, they sought to assess if daily doses of CBD over 10-days affected liver health. For this aspect of the study, researchers administered human equivalent doses of 5, 15 and 50 mg/kg per day for 10 days. This 5 mg/kg dose was based on the initial recommended dose for individuals taking EPIDIOLEX. A dose of 5 mg/kg per day of CBD would equate to consuming roughly 340 mg of CBD per day in a 150 lb adult, or over half of one of 6° Wellness’ 600 mg bottles. Three days into testing all of the animals in the 50 mg/kg group had to be put down due to symptoms of severe toxicity. However, keep in mind that to reach this dose, a 150 lb individual would potentially have to take 3,400 mg of CBD daily to elicit this effect. 

All the animals in the lower dose groups survived the 10-day treatment period and did not exhibit any visible signs of toxicity. In the high dose group, liver cells showed signs of extreme swelling but this wasn’t observed in the low dose group. Further, in assessing for markers of liver damage, there were no significant elevations in either of the lower dose groups, but total Bilirubin was elevated in the high dose 50 mg/kg group. These results imply that following daily doses of 50 mg/kg can cause liver swelling and damage, but at the low dose of 5 mg/kg there were no signs of liver inflammation or damage.

So, what does all of this mean? 

I know… that is a lot of information to take in. So, let’s summarize the main findings of this study in just a few sentences. The low doses administered in this study produced little if any indication of liver inflammation or damage following either a single dose of 20 mg/kg or 10-days of 5 mg/kg of CBD. At higher single and daily doses of CBD, symptoms of liver inflammation and damage were present. Nevertheless, don’t forget that for these doses to be achieved in a 150 lb human they would need to consume either 13,640 mg in a single dose or 3,400 mg/day over 10 days CBD to achieve these effects.

Can CBD and Acetaminophen be Taken Together? 

In follow-up to the first study, the article titled: “Paradoxical Patterns of Sinusoidal Obstruction Syndrome-Like Liver Injury in Aged Female CD-1 Mice Triggered by Cannabidiol-Rich Cannabis Extract and Acetaminophen Co-Administration” aimed to assess if taking CBD extract and acetaminophen, the main active ingredient in TYLENOL, together produced any negative side-effects on the liver (Ewing et al. 2019b). It is well established that high doses of acetaminophen can damage the liver (Larson 2007). And as we previously discussed it was also found that extremely high doses of CBD extract can produce similar damage. To assess this, researchers administered human equivalent doses of 10 and 25 mg/kg per day, equivalent to a 150 lb person taking 682 mg and 1,704 mg CBD respectively, for three days followed by a large dose of acetaminophen on the fourth day. In the 10 mg/kg group, it was found that there was a significant interaction effect between CBD and acetaminophen resulting in a nearly 40% mortality rate of the animals. It was found that this mortality resulted from large scale oxidative stress triggering liver cell death. However, this was not observed in the 25 mg/kg CBD group. In this group, there was a 0% mortality rate suggesting a paradoxical dose-dependent effect.

So, what do we take away from this second article? Well, first and foremost there is strong evidence to suggest that administration of CBD in high doses can interact with the common over the counter drug acetaminophen, like TYLENOL, that could potentially produce harmful effects. However, it’s important to put into context both the doses of CBD and acetaminophen used in this study. To reach the low dose of CBD used in this study, a 150 lb individual would have to take more than an entire 600 mg, 2oz bottle in one sitting (we don’t recommend doing that) for three consecutive days followed by 2,200 mg of acetaminophen at once. That would be the equivalent of taking 7 regular strength TYLENOL all at once. On their website, TYLENOL recommends taking 2 regular-strength tablets every 4-6 hours and to not exceed more than 10 tablets in 24-hours. That means to achieve this dose an individual would only have to take 70% of the maximum daily recommended dose at once to experience these effects. These are important findings, as many people who are taking CBD for pain relief may also be taking other drugs such as TYLENOL, and although either one in isolation is relatively safe, the two combined could possibly lead to toxic effects. 

What are some of the major limitations of these studies? 

The studies are somewhat limited by the content of the CBD extract used. The extract was not pure CBD and still contained concentrations of other cannabinoids like THC. Further, to produce the concentrate hexane was used as the extraction solvent. While the majority of the hexane was boiled off at 80°C to activate the cannabinoids there was still residual hexane (< 0.5%) present in the final extract, which is quite a bit. 0.5% would be the same as half  the amount of CBD in a 600mg, 2oz bottle of CBD (600mg CBD in 60 ml of oil = 1% CBD). It has been well known for more than 30-years that hexane is toxic to the liver, even at low concentrations, as described in “Hepatotoxic effects elicited by n-hexane or n-heptane” published back in 1988 (Goel et al. 1988). It’s possible that some of the toxic effects observed in these studies could be in part due to hexane exposure. Unfortunately, many companies providing CBD extracts use hexane in their extraction process as well, because it is easy, and very cheap. Now, you’re probably wondering “Is there any hexane present in the products provided by 6° Wellness?”. The short and long answer to that is… absolutely not. We use a CO2 extraction method, which leaves no volatile residues. Further, our products are tested by an independent third-party lab for not only hexane residuals but many other residual chemicals as well. As always, we want to ensure that we provide you with the highest quality product possible.

Final Thoughts

While it would take an extraordinary amount of CBD alone, or moderate doses of CBD and acetaminophen together to produce the effects described in these studies, it is always important to consider all medications and supplements you are taking at the same time. Unfortunately, research in this area is still limited. If you’re worried about cross-reactive effects of your medications and supplements, always consult your personal physician before adding it to your daily routine so they can monitor your health and any acute changes in your personal physiology. 

It is always important to remember that you can have too much of a good thing. While CBD has many proposed benefits, when consumed in extreme amounts it could potentially have negative side effects. Just like Ibuprofen and TYLENOL can help subside inflammation and pain, both can cause damage to the kidneys and liver if consumed in excess. Therefore, we recommend you always track your CBD intake, and only use pure products from 6° Wellness verified by a third party laboratory. Your health is always our top priority, and that is why we strive to provide you with the highest quality products possible. 

The media and science alike have a tendency to exaggerate scientific findings, and we know research articles can sometimes be intimidating to interpret. Their titles can be long and complex, and sometimes it’s difficult to make sense of the doses and methods being used. Don’t let that scare you, take ownership of your health and make an effort to dig deeper than the surface. If there is ever an article on CBD and health that you need help interpreting reach out to us at hello@sixdegreeswellness.com and we will do our best to provide our unbiased interpretation in future blog posts like this.

Looking for more 6° Wellness Content? 

Website: www.sixdegreeswellness.com 

Instagram: @6degreeswellness

Podcast: CBD Deep Dive anchor.fm/6degrees 

Jonny Lisano, Ph.D

JONNY LISANO, Ph.D.

Jonny received his Ph.D. from the University of Northern Colorado (UNC) in Exercise Physiology.  During his time at (UNC) he and his advisor established the first cannabis and exercise performance laboratory in the nation.  Jonny’s early research pertaining to cannabis focused on the assessment of how the long-term use of cannabis products in physically active individuals affected parameters of overall health and exercise performance.  As he progressed into the field of cannabis research his focused shifted from exercise performance to that of how CBD affects immune function in physically active individuals who are using cannabis products.

Jonny has always been an advocate for living a healthy lifestyle and believes CBD can be an integral part of that.  His focus at 6° Wellness is to provide and explain the most current scientific knowledge pertaining to cannabis in a way everyone can understand, and providing recommendations on how the products we offer can fit into your lifestyle.

In his free time Jonny enjoys training for competitive obstacle course races, hiking the beautiful Colorado backcountry, and partaking in the occasional beer from the local craft beer scene.


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Disclaimer: Part of our mission is to always present the latest cannabinoid research; however, none of this is intended to represent the safety or efficacy of our products. These statements and our products have not been evaluated by the FDA, and our products are not intended to diagnose, prevent, treat or cure any disease. You should consult your physician or other health care professional before taking CBD to determine if it is right for your needs.

Photo by Sergei Akulich on Unsplash

CBD: We know it comes from cannabis, but how and why is it made? 

Written by: Dr. Jonny Lisano, Ph.D.

In this article, we will discuss the basic physiology behind the making of cannabidiol (CBD) and some theorized reasons why plants of the cannabis family, like hemp and marijuana, might produce phytocannabinoids like CBD.  

How does Cannabis Sativa L. Produce CBD? 

When referring to products within the cannabis industry, particularly those containing cannabidiol (CBD), we typically classify them as being either hemp or marijuana-derived. Recent evidence suggests that there are distinct genetic differences between hemp and marijuana (Sawler 2015), but due to generations of select cultivation and crossbreeding there is not enough of a difference to classify them as different plants. Currently, both hemp and marijuana are classified as the same plant Cannabis Sativa L., because of this, the only clear distinction between hemp and marijuana is that based on legality.

Hemp, of course, is classified within the United States as having less than 0.3% delta-9-tetrahydrocannabinol (THC) and anything with more than 0.3% THC is classified as marijuana. The reason hemp and marijuana are so sought after is for their production of the compounds known as phytocannabinoids, or more commonly referred to as cannabinoids. Hemp is sought after for its high CBD content, while marijuana is most desired for its high production of THC. The endocannabinoid system, on which these compounds act, is actually so named because it was first discovered through receptors in the central nervous system interacting with THC.  

Cannabidiol, also known more commonly as CBD, is one of more than 100 identified phytocannabinoids produced by the cannabis plant Cannabis Sativa L. (Russo 2011). The majority of the active components in cannabis products are produced in structures called trichomes in the plant (Russo 2011). In these trichomes, the first step in producing CBD is the creation of cannabigerolic-acid (CBGA) (Thomas 2016). The cannabinoid CBGA is a precursor to the formation of multiple cannabinoids, including CBD, THC, cannabichromene (CBC) and cannabigerol (CBG) (Thomas 2016). The formation of CBGA begins with building blocks of Coenzyme A and a fatty acid. The use of fatty acids in the production of cannabinoids is a primary reason why cannabinoids like CBD are fat-soluble. Following multiple intermediate steps, CBGA is eventually derived from olivetolic acid and geranyl pyrophosphate (Thomas 2016). Side note: the “ger” in cannabigerolic-acid comes from the “ger” in geranyl pyrophosphate. 

As stated previously, CBGA can then be used for the eventual formation of CBD. First, CBGA is converted to the acidic form of CBD, cannabidiolic acid (CBDA). This process is performed by CBDA synthase (Taura 2007, Thomas 2016).  However, the cannabinoid CBDA is not yet the CBD that we all know and love. For CBD to be produced the next step that must occur is the chemical decarboxylation of CBDA. For those of you not well versed in the terminology of chemistry, decarboxylation simply refers to the removal of CO2 from CBDA. Once this CO2 is removed, which is typically done through the use of heat, CBD has now been formed (Hartsel 2016). It would make sense then that CBD, does not naturally occur in abundantly high quantities of either marijuana or hemp, but rather is found as the precursor CBDA. This is why the cannabis industry has developed effective ways, like supercritical CO2 extraction, to efficiently extract and decarboxylate cannabinoids like CBD in highly concentrated quantities.  

The CBD synthesis process within cannabis can be seen in the figure below in it’s entirety.

Why does Cannabis Sativa L. produce cannabinoids like CBD? 

There are mixed schools of thought on why Cannabis Sativa L. produces cannabinoids. One thought is that the cannabis plant produces the active components as a natural defense mechanism against parasites pests and potential predators.  However, many of the insects that would threaten the plant are devoid of an endocannabinoid system, and thus would be immune to any potential negative effects. Another school of thought is that Cannabis Sativa L. produces these cannabinoids to prevent mammalian herbivores and omnivores from eating it; however, while these mammals do possess an endocannabinoid system, cannabinoids in their raw, acidic form are not physiologically active. Thus, similarly to insects, these mammals would not feel any effects from these cannabinoids and would have no reason to be deterred from eating the plant. So why then does cannabis produce these cannabinoids?  

 If you were to say that cannabinoids are produced by the cannabis plant to appease us, the “human overlords”. Well, you might actually be right… among biologists studying the Cannabis Sativa L. plant itself, this is one of the more popular theories. The relationship between humans and cannabis has existed for thousands of years (Sawler 2015). This has spurred the formation of a symbiotic relationship between humans and the plant. Humans grow and cultivate cannabis for its therapeutic effects, ensuring the survival of the cannabis plant at the same time.  Scientists believe that due to the longterm cultivation and selective breeding of the Cannabis Sativa L. plant, we have naturally encouraged the plant to produce more cannabinoids over time, through the increased gene expression of the enzymes necessary to create the cannabinoids like CBD, THC, and CBGA. Inadvertently because of these generations of selective breeding for high cannabinoid content scientists are still unsure as to why the cannabis plant produces cannabinoids. 

Looking for more 6° Wellness Content? 

Website: www.sixdegreeswellness.com 

Instagram: @6degreeswellness

Podcast: CBD Deep Dive anchor.fm/6degrees 

Jonny Lisano, Ph.D

JONNY LISANO, Ph.D.

Jonny received his Ph.D. from the University of Northern Colorado (UNC) in Exercise Physiology.  During his time at (UNC) he and his advisor established the first cannabis and exercise performance laboratory in the nation.  Jonny’s early research pertaining to cannabis focused on the assessment of how the long-term use of cannabis products in physically active individuals affected parameters of overall health and exercise performance.  As he progressed into the field of cannabis research his focused shifted from exercise performance to that of how CBD affects immune function in physically active individuals who are using cannabis products.

Jonny has always been an advocate for living a healthy lifestyle and believes CBD can be an integral part of that.  His focus at 6° Wellness is to provide and explain the most current scientific knowledge pertaining to cannabis in a way everyone can understand, and providing recommendations on how the products we offer can fit into your lifestyle.

In his free time Jonny enjoys training for competitive obstacle course races, hiking the beautiful Colorado backcountry, and partaking in the occasional beer from the local craft beer scene.


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Disclaimer: Part of our mission is to always present the latest cannabinoid research; however, none of this is intended to represent the safety or efficacy of our products. These statements and our products have not been evaluated by the FDA, and our products are not intended to diagnose, prevent, treat or cure any disease. You should consult your physician or other health care professional before taking CBD to determine if it is right for your needs.

Photo Credit: Max Seigal

What are some ways that you can use 6° Wellness’ full spectrum 600 mg hemp extract?

Have you recently purchased or have been contemplating buying 6° Wellness’ full spectrum 600 mg hemp extract, but aren’t sure how to use CBD oil. In this article we will discuss some of 6° Wellness’ favorite ways to incorporate our 600 mg oil into our daily life.  

Written by: Dr. Jonny Lisano, Ph.D. 

The Tried and True: Oral Tincture

One of the most popular ways to use 6° Wellness CBD oil is as an oral tincture. If you are new to using CBD you might ask, “What is a tincture?”. Well, that is a great question. In general, a tincture is a plant concentrate that contains active ingredients that are suspended in oil and are taken orally by dispensing the desired amount into your mouth. The 6° Wellness 600 mg extract is derived from hemp, contains active ingredients like phytocannabinoids (such as CBD) and terpenes, and is suspended in MCT oil. 

To use 6° Wellness oil extracts as an oral tincture simply fill the pre-marked dropper to your desired dose, dispense the oil under your tongue and just let it naturally dissolve. Repeat as necessary if your desired dose is larger than 10 mg, or 1 mL. The MCT oil that our extract is suspended in has a very warming taste and should not have any bitter off taste. 

Coffee

If you’re like me, your morning cup of coffee helps jumpstart your day each and every morning and gives you the energy boost you need to get out the door and tackle the day ahead.  One of my personal favorite ways to consume my 6° Wellness CBD oil is as a part of my morning coffee; however, keep in mind that coffee consists mainly of water. Water and oil won’t naturally mix together. If you’re going to add your CBD oil to your morning cup o’ Joe, I’d suggest first dissolving your CBD in small amount of cream, give it a quick blast of heat in the microwave, quickly stir and then add it to your coffee.  Or, if you’re on the go you can simply add your CBD oil straight into your latte from your favorite coffee shop!

Tea 

Not a coffee person, but still like a warm dose of caffeine during your day? Try adding your CBD oil to a cozy, warm cup of tea. Just remember, tea like coffee, consists of mostly water. To get your CBD oil to fully dissolve we suggest using a little bit of cream to help. 

Smoothie

Whether you’re on the go or looking for an easy post workout meal, a smoothie is a fantastic way to consume your 6° Wellness CBD oil. Simply add in your desired amount of oil with your favorite smoothie ingredients and blend.  As we’ve discussed in a previous blog post, we suggest consuming your CBD oil with food containing fats. Research has shown that not only will this increase your absorption of CBD but also increase the bioavailability! You can read more on that here. Our suggestion to easily and deliciously increase the fat content of your smoothie is to add in a scoop of your favorite nut butter (peanut, almond, etc.).

Oatmeal

If you’re looking for for a heartier and warmer meal option to consume your CBD oil try adding it to your bowl of oatmeal. We recommend preparing your oatmeal exactly how you normally would and just before you eat it stir in your desired amount of CBD oil. Not only will you be getting a delicious bowl of oatmeal full of great nutrients and complex carbs that will keep you full, but you’ll also be getting your CBD. I’d call that two birds with one stone!

Protein Pudding

If you haven’t heard of Musclelicious Foods’ protein puddings, you don’t know what you’re missing out on. Not only are they a stand-up family run operation, but the owners only make their products using the highest quality ingredients (just like 6° Wellness). Their puddings are delicious and come in a variety of flavors, and now some of their puddings come with 6° Wellness CBD oil already mixed in! Their CBD protein puddings have a little over 12 mg of CBD in every cup! If that’s not enough for you you can always mix in more 6° Wellness CBD oil yourself. 

Salad Dressing

If you like to make your own salad dressings, this is a great opportunity to add a fun, new way to use you 6° Wellness CBD oil. Make your dressing as you usually would and just add in your desired amount of CBD oil.  Just keep in mind that if you make your homemade dressing in large batches that you plan to use over time, that oils other than MCT oil may degrade your CBD over time. Read more about it here in a previous blog post, where we discuss why MCT oil is the best oil for CBD extracts. 

Summary

It just goes to show that there are multiple ways to consume your 600 mg CBD oil from 6° Wellness. Whether its as a part of your morning coffee, post workout smoothie or part of your salad; you don’t have to limit yourself to using it only as a tincture (although there is nothing wrong with using as a tincture). Have fun with your CBD and experiment using it in different ways! The more ways you learn to use your CBD products the easier it will be to make it a part of your daily lifestyle. 

What are some of your favorite ways to use your CBD oil? Let us know in the comments section below. Who knows, maybe we’ll feature your favorite method in a future blog post or podcast?!

Looking for more 6° Wellness Content? 

Website: www.sixdegreeswellness.com 

Instagram: @6degreeswellness

Podcast: CBD Deep Dive anchor.fm/6degrees 

Jonny Lisano, Ph.D

JONNY LISANO, Ph.D.

Jonny received his Ph.D. from the University of Northern Colorado (UNC) in Exercise Physiology.  During his time at (UNC) he and his advisor established the first cannabis and exercise performance laboratory in the nation.  Jonny’s early research pertaining to cannabis focused on the assessment of how the long-term use of cannabis products in physically active individuals affected parameters of overall health and exercise performance.  As he progressed into the field of cannabis research his focused shifted from exercise performance to that of how CBD affects immune function in physically active individuals who are using cannabis products.

Jonny has always been an advocate for living a healthy lifestyle and believes CBD can be an integral part of that.  His focus at 6° Wellness is to provide and explain the most current scientific knowledge pertaining to cannabis in a way everyone can understand, and providing recommendations on how the products we offer can fit into your lifestyle.

In his free time Jonny enjoys training for competitive obstacle course races, hiking the beautiful Colorado backcountry, and partaking in the occasional beer from the local craft beer scene.


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Disclaimer: Part of our mission is to always present the latest cannabinoid research; however, none of this is intended to represent the safety or efficacy of our products. These statements and our products have not been evaluated by the FDA, and our products are not intended to diagnose, prevent, treat or cure any disease. You should consult your physician or other health care professional before taking CBD to determine if it is right for your needs.

Should I take my CBD on an empty stomach or with food?

In this article we answer the questions of’ “Does my body absorb CBD extract differently if I consume it on an empty stomach or with food?” and, “If there is a difference, which way is better?” using findings from a recent scientific study assessing the pharmacokinetics of CBD consumed in a fed or fasted state. 

Written by: Dr. Jonny Lisano, Ph.D. 

The research on how cannabidiol (CBD) and the other active components in marijuana and hemp products is growing; however, the research available on how to consume CBD products is still very limited. One topic that has frequently come up in conversations that I have had is, “Does it matter if I consume my CBD products on an empty stomach, or should I take it with food?”. Well, until now the research available has not provided a clear answer to this question.  A recent study from the University of Minnesota sought to provide novel insight in this area by assessing the pharmacokinetics of orally ingested purified CBD when consumed in a fasted or fed state. 

The Basics of Pharmacokinetics: 

However, before we dive into the results of this study let’s first briefly discuss what the field of pharmacokinetics is and some key terms used in research within this content area.  Putting it very simply, pharmacokinetics is a branch of pharmacology that seeks to describe the movement and distribution of drugs or compounds throughout the body. Within the realm of pharmacokinetics there are a few key terms that are often used to describe and compare the movement of these drugs and compounds throughout the body.  

  • Maximum concentration (Cmax): This is the maximum concentration of the drug/compound (in this case CBD) observed in the blood plasma following administration. This one is pretty intuitive, the higher the maximum concentration the more of that compound there is in the blood.  
  • Time to maximum concentration (Tmax): This is the time it takes for the compound to reach maximum concentration following administration. Less time to maximal concentration means the quicker that compound reached peak concentration in the blood.
  • Area-under-the-curve (AUC): in order to determine this variable multiple data points are needed. These data points are collected over regular intervals in the hours following administration of the drug or compound. The data points are then graphed to determine the total drug/compound exposure over the monitored time period. An example of this can be seen in Figure 1.  As can be seen in Figure 1, the AUC for Naringenin is greater than that of Hesperitin over the monitored 24-hour period. A greater AUC means that there’s greater exposure to that drug/compound. So, in this example The drug Naringenin would have greater exposure within the body compared to Hesperitin.  

Figure 1: Area Under the Curve Example

Obtained from Science Direct 

  • Volume of distribution (Vd): This is a very complex and abstract concept when discussing pharmacokinetics; but to put it simply, the volume of distribution is a ratio between the amount of compound taken and the concentration of that compound within the plasma.  Based on this ratio, this will give us an indication of how extensively a compound is distributed throughout the rest of the body compared to the plasma. A high volume of distribution means that a compound is going to be distributed more to the tissues and not stay in the plasma, while a low volume of distribution means that the compound will stay localized in the plasma.
  • Plasma oral clearance (PC): This parameter is used to describe the volume of plasma that the compound is completely removed from per unit of time, typically expressed in hours.  This will tell you how quickly the compound is removed from the plasma. A higher plasma oral clearance means quicker removal.  

Alright, I know that was a lot of information that you just went through on the basics of pharmacokinetics, but a good understanding of those few terms will help you better understand the results of this study.

Study Results:

The study had a total of eight participants suffering from difficult to control epilepsy. These participants were recruited to participate in two separate testing conditions by consuming a specific amount of purified CBD while fasted state or with food.  For both conditions participants arrived 10-hours fasted and had resting blood samples taken prior to either consuming 300mg of 99% pure CBD with water (fasted) or consuming 300mg of CBD with water and a high-fat breakfast (fed) of 840-860 calories (500-600 of the calories coming from fat).  These participant’s blood was then taken at 0.5, 1, 2, 2.5, 3.5, 4, 5, 6, 24, 48, and 72 hours post CBD consumption and analyzed for plasma concentration of CBD. All eight participants went through both trial conditions separated by roughly 2-weeks between trials. In Figure 2 below you can see the average concentrations of CBD in the plasma over that 72-hour period. The red line represents the results from the fed trial while the darker line represents the fasted trial. 

Figure 2: Pharmacokinetic Graph of Consuming CBD in a Fasted or Fed State

In fed state participants had demonstrated a significantly greater maximum concentration (Cmax) than when they consumed their CBD in the fasted state.  In both trials the time to maximal concentration (Tmax) varied between 1 to 6-hours, but on average participants reached Tmax quicker in the fed trial. The fed trial had an average time to maximal concentration of 2.4-hours compared to 3.2-hours in the fasted state. These results show that not only did participants in the fed trial reach a higher Cmax but also had a quicker Tmax as well. 

Intuitively, you might look at Figure 2 and think, “Well clearly the area under the curve (AUC) in the fed state is greater than that of the fasted state.” Guess what? You’d be correct! Statistically the AUC was significantly greater in the fed state.  This means that over the monitored 72-hour period that participants who consumed their CBD with food had greater exposure to CBD than when they only consumed CBD with water. Even though they took the exact same amount of purified CBD (300mg) in the fed state as they did in the fasted state!  

The volume of distribution was considered high in both the fasted and fed trials; however, the volume of distribution was greater in fasted participants. While this may not sound like a desirable result for the fed condition, both conditions still had high volumes of distribution! This means that regardless of the method of ingestion, when CBD is absorbed by the bloodstream it is highly dispersed to your tissues and does not remain in the blood. That is good, because we want CBD to be able to interact with the endocannabinoid system of our body. Also, when assessing the plasma oral clearance, fed individuals had a significantly lower clearance rate than fasted individuals. One explanation the researchers offer for why we see these effects on the volume of distribution is that consuming CBD with food is actually increasing the bioavailability of CBD! Which is a very good thing. 

Obviously this study did not take into account the co-ingestion of CBD with lower fat content meals, and I’m not telling you to go out and consume 70 grams of fat every time you take your CBD, but results from this study do indicate that consuming CBD with a meal containing fat increases both the absorption and bioavailability of CBD in the body. Potentially increasing the effectiveness of your CBD.  So, I’ll leave you with this, consuming CBD with a meal containing fats may get you more bang for your CBD buck.  

Looking for more 6° Wellness Content? 

Website: www.sixdegreeswellness.com 

Instagram: @6degreeswellness

Podcast: CBD Deep Dive anchor.fm/6degrees 

Jonny Lisano, Ph.D

JONNY LISANO, Ph.D.

Jonny received his Ph.D. from the University of Northern Colorado (UNC) in Exercise Physiology.  During his time at (UNC) he and his advisor established the first cannabis and exercise performance laboratory in the nation.  Jonny’s early research pertaining to cannabis focused on the assessment of how the long-term use of cannabis products in physically active individuals affected parameters of overall health and exercise performance.  As he progressed into the field of cannabis research his focused shifted from exercise performance to that of how CBD affects immune function in physically active individuals who are using cannabis products.

Jonny has always been an advocate for living a healthy lifestyle and believes CBD can be an integral part of that.  His focus at 6° Wellness is to provide and explain the most current scientific knowledge pertaining to cannabis in a way everyone can understand, and providing recommendations on how the products we offer can fit into your lifestyle.

In his free time Jonny enjoys training for competitive obstacle course races, hiking the beautiful Colorado backcountry, and partaking in the occasional beer from the local craft beer scene.


chris-lawton-5IHz5WhosQE-unsplash-1200x800.jpg

Disclaimer: Part of our mission is to always present the latest cannabinoid research; however, none of this is intended to represent the safety or efficacy of our products. These statements and our products have not been evaluated by the FDA, and our products are not intended to diagnose, prevent, treat or cure any disease. You should consult your physician or other health care professional before taking CBD to determine if it is right for your needs.

Will the quality of my CBD extract change over time?

Written by: Dr. Jonny Lisano, Ph.D.

If you currently use CBD products, a question that may have crossed your mind (or maybe not!), is what is the shelf life of these products? Can the content of your CBD hemp extract really change over time? With the approval of the 2018 Farm Bill in the United States, there has been a boom of cultivation, sale, and consumption of cannabidiol (CBD) products derived from industrial hemp,   but these products are not subject to regulation for their content and quality by the Food and Drug Administration (FDA). As a consumer, you must take it upon yourself to understand the quality and stability of these products over time. We’re here to help you with that. 

First, let us review the main active components in hemp extracts. Cannabinoids, like CBD and small amounts of THC (delta-9-tetrahydrocannabinol), are the most well-known active ingredients in hemp. Terpenes are the other active ingredients that have been receiving attention as of late. We know cannabinoids interact with the endocannabinoid system within the human body to produce their effects, but what purpose do the terpenes serve? In the cannabis plant, terpenes are believed to act as a defense system, deterring predators by producing an undesirable bitter taste (Russo & Marcu 2017). However, recently there is growing evidence that these terpene compounds can produce physiological effects in humans as well (Gallily et al. 2018)

Does the content of the cannabinoids and terpenes change over time?  The short answer to this question is yes.  Just like any other biological substance we consume, hemp and cannabis extracts change over time, but what specifically is changing and what are some of the key factors driving these changes? 

What is changing in these products?

THC: We know THC isn’t the major cannabinoid we are concerned with when it comes to hemp extracts, but it is still important to discuss, especially if you use other cannabis products higher in THC. The THC molecule is relatively unstable and has the propensity to react with other elements leading to THC breakdown if not properly stored.  A 2012 study found that the THC concentration in oil steadily decreased over time. Over a four-year period, a loss of 84-90% of its initial THC content occurred, losing on average 21-23% of its THC content per year (Trofin et al. 2012). Depending on how you feel about THC, this may be either a desirable or undesirable trait of long-term storage of cannabis products.  But what about CBD, the main cannabinoid we are concerned about with hemp extracts?

CBD: Similar to THC, the CBD content in oil changes over time.  In products containing 15-16% CBD, it was observed that 11% of the initial CBD was lost over the first year, with an average loss of 2.76% of total CBD every three months (Trofin et al. 2012). However, unlike THC which decreased 84-90% of its initial content over 4-years, CBD only lost 40% of its initial content over that same 4-year span (Trofin et al. 2012).  This demonstrates that while CBD content does decrease over time, it occurs at a much slower rate than THC.

CBN: Depending on how familiar you are with cannabis products, you may or may not have heard about CBN, also known as cannabinol. CBN is typically found in higher concentrations of aged cannabis products as it is a product of THC breakdown (Trofin et al. 2012).  While not as potent as THC, CBN does still have moderate intoxicating effects (Casajuana Koguel et al. 2018).  It has been observed that a steady decrease in THC concentration was offset by a steady increase in CBN concentration (Trofin et al. 2012). However, there is not a 1:1 conversion relationship of THC to CBN, as THC can be degraded into other byproducts other than CBN (Trofin et al. 2012)

Terpenes: Terpenes, as discussed earlier, are another active component found within hemp extracts. In a study assessing the content and stability of hemp oils distributed within the United Kingdom,  it was found that the terpene content was susceptible to change in the presence of light (Pavlovic et al. 2018).  Limiting exposure to light is an important factor to consider in the storage of your hemp extract products.  There is a growing amount of evidence that CBD and the other active compounds in hemp extract work best together producing what’s referred to as the ‘entourage effect’. Proper storage of your product is essential (Calvi et al. 2018, Galilly et al. 2018)!

What is causing these changes?

Light Exposure: Light is one of the environmental conditions that can affect the content of your product. Light has the capacity to interact with reactive oxygen causing photooxidation of cannabinoids and terpenes alike (Trofin et al. 2012, Pavlovic et al. 2018).  This is why we recommend you store your hemp extract in a place that will not receive direct light exposure.   

Air Exposure: The second component necessary for photooxidation is air.  Make sure that whenever you finish using your 6° Wellness products that you tightly secure the lid back on to minimize air exposure.  However, oxidation products can come from more than just air. The breakdown of fats found within oils also has the same effect.

Type of Oil: Not all oil products are created equally when concerning the stability of your cannabis products.  In the study assessing the long-term stability of CBD oil extracts from the United Kingdom, there were a total of 15 different samples collected and tested. Of those 15 products, six were suspended in olive oil, eight were suspended in hemp seed oil and one was suspended in MCT (medium-chain triglyceride) oil.  The sample suspended in MCT oil was the only product found to have little, if any, fat oxidation products (Pavlovic et al. 2018). This means that suspending hemp extract in MCT oil will preserve quality by preventing the formation of oxidizing products.  

I know as you read that you just asked, “Well, are 6° Wellness products suspended in MCT oil?”. The answer to that question is a resounding, “YES!”. 

As a consumer, you not only deserve to have the best products but also the assurance that the products will be consistent across its use period.  To maximize the potential of your 6° Wellness products, we recommend you keep them stored in a cool, dry place that does not receive direct sunlight.  Furthermore, the final aspect of product quality assurance relies on you.  

As we discussed previously the content of hemp extract oils can change over time. While you might think it’s more cost effective to purchase larger hemp extract products, always keep in mind how long it will take you to use the entirety of the product.  For example, say you use 20mg of extract a day. The 600mg bottle offered at 6° Wellness would last you a total of 30-days. However, if you wanted to buy in bulk a 6,000mg bottle would last you at that same dose for 300-days. By the end of that 300-day period approximately 10% of the initial CBD concentration would be lost and instead of receiving 20mg on that final dose you’d receive 18mg.  While that is not a drastic change, we still want you to get the most out of our products. It’s similar to buying any other food item. 

We recommend buying enough product to last you 1-3 months based on your daily use.  Buying the proper amount and storing your CBD in a cool, dry place in the dark will ensure that you’re getting the most out of your 6° Wellness hemp extract throughout its duration of use. 

6° Wellness strives to provide you with clear, concise information for CBD use. We achieve this through science-based research using our products. We will continue to provide you with the most reliable and safe information possible on how you can incorporate CBD supplements into your daily life.  

Looking for more 6° Wellness Content? 

Website: www.sixdegreeswellness.com 

Instagram: @6degreeswellness

Podcast: CBD Deep Dive anchor.fm/6degrees 

References: 

Calvi, L., Pentimalli, D., Panseri, S., Giupponi, L., Gelmini, F., Beretta, G., Vitali, D., Bruno, M., Zilio, E., Pavlovic, R., Giorgi, A. 2018. Comprehensive quality evaluation of medical Cannabis Sativa L. inflorescence and macerated oil based on HS-SPME coupled to GC-MS and LC-HRMS (q-exactive orbitrap) approach. J. of Pharma. Biomed. Analysis, 150: 208-219.  

Casajuana Koguel, C., Lopez-Pelayo, H., Balcells-Olivero, M.M., Colom, J., Gual, A. 2018. Psychoactive constituents of cannabis and their clinical implications: a systemic review. Adicciones, 30(2):140-151.

Gallily, R., Yekhtin, Z., Hanus, L.O. 2018. The Anti-Inflammatory Properties of Terpenoids from Cannabis. Cannabis Cannabinoid Res. 3(1): 282-290.

Pavlovic, R., Nenna, G., Calvi, L., Panseri, S., Borgonovo, G., Giupponi, L., Cannazza, Giorgi, A. 2018. Quality Traits of “Cannabidiol Oils”: Cannabinoids Content, Terpene Fingerprint and Oxidation Stability of European Commercially Available Preparations. Molecules, 23(5): 1230. 

Russo, E.B., Marcu, J. 2017. Chapter Three – Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads. Adv. In Pharmacol., 80: 67-134.  

Trofin, I.G., Dabija, G., Vaireanu, D., Filipescu, L. 2012. Long-term Storage and Cannabis Oil Stability. Rev. Chim., 63(3): 293-297.

 

 

 

 


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