Cannabinoids: CBD, CBN, THC. Also HEMP & Marijuana (Cannabis)

Products from the cannabis plant offer many health benefits of interest to ApoE4 carriers and can enhance a program addressing lifestyle strategies. Cannabis products come in many forms with numerous delivery methods: tablets/capsules, edibles, beverages, vaping oil, dermal lotions/patches, sublingual tinctures, suppositories, and more, no need to smoke a joint. THC is a cannabinoid that is the psychoactive component of marijuana that produces a high. CBD, another cannabinoid, modulates several biological functions and, in the right percentages, can counteract the psychoactive effects of THC. Cannabis products come in various ratios of CBD to THC to best target the effect a person is trying to obtain. Many products with THC produce a high, but some do not, especially those with a high CBD to low THC content. CBD products from hemp do not produce a high.

Cannabis is both hemp and marijuana, each containing a number of cannabinoids

The cited medical benefits of cannabinoids are many but it should be noted that legal constraints and the lack of profit incentive for drug companies, have constrained medical studies. Of the studies that exist, many are indicative of medical benefit, but often conclude further study is needed.

Fully exploiting the medical benefits of cannabis products may be long in coming, if ever. Pharmaceutical companies can’t patent a natural substance unless they turn it into a synthetic chemical first. Doctors in the United States can’t prescribe drugs that aren’t approved by the Food and Drug Administration (FDA) and doctors rarely recommend therapies that fall outside approved protocols and/or are unfamiliar with nontraditional therapies.

Nevertheless, many studies are encouraging, and there are even more anecdotes citing benefits. For many of us, there’s no time to wait for FDA approval, thus necessitating self-research for potential beneficial therapies. The deeper dive section below provides papers supporting the claims of some of the health benefits of cannabis products/cannabinoids.

There are no known studies that have singled out the ApoE allele to determine the effects of cannabinoids on the endocannabinoid system within ApoE4 carriers. However, cannabinoids have been cited to aid with numerous health issues for the general population, and these are the areas of greatest interest to ApoE4s:

• Alzheimer’s Disease

• Decreases Amyloid-beta plaque
• Offers neuroprotection and helps generate new neurons

• Inflammation
• Insulin Resistance
• Stress
• Sleep
• Hormonal balance

There are other health conditions where cannabinoids can be beneficial, such as cancer, Post Traumatic Stress Disorder (PTSD), Fibromyalgia, epilepsy, and more, but this Wiki article does not attempt to be all encompassing with regard to cannabis, only as it applies to areas of interest to ApoE4 carriers.

A guide to associated terms

To better navigate this subject and to make the best decisions, it helps to understand these common terms.

Cannabis

The plant family that includes both marijuana and hemp.

Marijuana

A cannabis plant that possesses psychoactive qualities (produces a high). Used recreationally for the high and for medicinal purposes.

Marijuana is illegal in all 50 states per federal law. It is recognized as legal for medical purposes (medical marijuana card required) in over half the 50 states. Marijuana is legal for recreational purposes in some states, per state law.

Marijuana comes from two strains: indica and sativa. Sativa strains produce more of a euphoric high, is a mood elevator, and therapeutically relieves stress. Indica strains relax muscles and work as general analgesics (pain relief), also helps with sleep.

Each state has its own unique list of conditions that qualify a person for a medical marijuana card, but the most common medical conditions are:

• Epilepsy and Seizure disorders - cannabidiol (CBD) has been found to significantly reduce seizure frequency
• Cancer - a balance of THC or CBD helps with pain, nausea, and appetite loss
• Multiple Sclerosis – aids with pain, insomnia, inflammation, muscle spasms, abdominal discomfort, and depression,
• Glaucoma
• HIV/AIDS – for appetite loss, nausea, and fatigue
• Neurodegenerative Diseases (Lou Gehrig’s Disease (ALS), Alzheimer’s, Parkinson’s, and Huntington’s) – improves cognition and mobility, relieving spasticity and rigid muscles, and more
• Pain - combining both THC and CBD tend to be most effective
• Nausea – THC helps, although too much worsens it
• Cachexia/Wasting Syndrome – especially for THC rich varieties
• Post-Traumatic Stress Disorder – high CBD varieties can aid with anxiety and panic episodes

For more in information, see Most Common Qualifying Conditions for Medical Cannabis

However, research into marijuana for medical application is restricted. The US Drug Enforcement Agency (DEA) considers marijuana a Schedule I drug, the same as heroin, LSD, and ecstasy, thus identifying it as likely to be abused and lacking in medical value. Because of that, researchers need a special license to study it. The US Food and Drug Administration (FDA) has not approved marijuana for medical treatment purposes although it has approved drugs derived from the marijuana plant. Marinol and Casemet are man-made versions of THC used to treat nausea and lack of appetite. Epidiolox is treatment for children’s epilepsy. A 4th drug, Sativex, a cannabis extract containing THC and CBD in a 1-to-1 ratio, is in clinical trials in the U.S. for pain with breast cancer. Sativex is already approved in more than 20 countries to treat muscle spasms from MS and cancer pain.

Even in states where marijuana is legal for recreational purposes, there are laws regarding age of consumption, where it can be consumed, restrictions on driving under the influence, and interstate transport. Employers and landlords may additionally dictate consumption restrictions regardless of state law. States that allow medical marijuana do tend to reciprocally respect medical marijuana cards from other states but transport through non-recognizing states or flying with marijuana is illegal. The U.S Transportation Security Administration (TSA) does not allow marijuana or products derived from marijuana on any flights.

Although legal, quality can be a concern. Especially when seeking assistance for medical conditions, it’s important to know that the product being consumed is free of harmful chemicals and toxins. There are no federal regulatory protections. Marijuana is now being grown using many modern day farming methods which includes growing plants in soils devoid of nutrient content and adding chemicals for rapid growth, pest resistance, and ease of harvest. Marijuana cannot be labeled “organic” by the US Department of Agriculture because it is still illegal at the federal level. Testing regulations vary from state to state: State-by-State Guide to Cannabis Testing Regulations Leafly's state-by-state guide to cannabis testing regulations

Third parties have taken on the organic certification role for marijuana. Additionally, independent laboratories that can test for potency/homogeneity and cannabinoid analysis quantitation. They can also test for potentially harmful contaminants, such as Salmonella, E. coli, as well as total yeast and mold quantification. There are poor quality products out there, so buyer beware, but a reputable cannabis company will be able to offer information regarding the research and content of their products.

Hemp

A variety of the cannabis sativa plant that is grown for various commercial and industrial uses. Although marijuana and industrial hemp are both members of the cannabis family and both contain tetrahydrocannabinol (THC), they are distinct strains. Hemp has a near negligible level of THC. A person cannot get high from the THC content in hemp nor can drug testing cannot detect THC from hemp products. Hemp can be grown to make fabrics, construction materials, biofuels, plastic composites and more. Hemp products for individual consumption include hemp protein powder, hemp seed oil, CBD oil, hemp lotion, hemp hearts, even hemp beer. All can be purchased legally, except for the beer if underage. Just because a product comes from hemp doesn’t mean it has substantive cannabidiol (CBD) or other cannabinoid content.

Cannabinoids

Or more technically correct, phytocannabinoids are the active ingredients found in cannabis (phyto means from a plant). The most prevalent and the most well-understood phytocannabinoids are THC and CBD, but there are over 100 other active cannabinoids in cannabis.

Some cannabinoids and their associated health benefits. Source: https://bengreenfieldfitness.com/article/supplements-articles/how-to-use-cbd-oil/

Cannabinoids are also produced naturally in the body, see endocannabinoids below. While the functions of these cannabinoids within the body are wide-ranging, it is believed that their primary function is to promote homeostasis (a relatively stable state of equilibrium).

THC

Delta-9-tetrahydrocannabinol, or Δ9-Tetrahydrocannabinol, or more simply and commonly, tetrahydrocannabinol. THC is a cannabinoid. THC is the principal psychoactive component of cannabis, it’s what produces the high. Marijuana of the 1960s typically had a THC content of between 3% to 5%, today THC content has been cited to be as much as 35%.

CBD

Cannabidiol, a cannabinoid. CBD is non-psychoactive, it does not have the intoxicating effects of THC. CBD can actually counteract the psychoactivity of THC and combat unpleasant effects of THC such as paranoia, anxiety, over-excitability, or memory-loss. CBD acts on completely different receptors and enzymes than THC. CBD is associated with a long list of health benefits and is considered the healing component of the cannabis plant.

CBD is found in both marijuana and hemp, although percentages vary widely.

Historically, marijuana was cultivated for THC content, but when CBD was found to have positive benefits, some marijuana strains started being cultivated for CBD content too. Marijuana products are sold with various CBD to THC ratios but can only be sold in dispensaries in states where marijuana is legal for medical and/or recreational purposes. However, these marijuana derived products can be freely and legally researched on the internet before entering a dispensary.

In the United Sates, CBD from hemp is freely sold at certain retail outlets, over the internet, and consumed, but the legalities are not crystal clear. The laws target cultivation and sales, possession and consumption is not a legal concern. The Agricultural Act of 2014 authorized growing industrial hemp, defined as marijuana with a THC content of 0.3 percent or less, for agricultural research purposes where permitted under state law. With that, certain states began growing and selling hemp products, including CBD oil. The products are proliferating despite the fact that the US Food and Drug Administration (FDA) says CDB oil cannot be marketed as a dietary supplement. The United States Controlled Substances Act excludes certain parts of the cannabis plant that are incapable of producing the psychoactive “high” thus allowing the import and export of such products from the United States legal, yet CBD products have at times been blocked by the US Customs and Border Patrol (CBP) for export. Until recently, the DEA considered all cannabis products, including CBD, Schedule I substances along with heroin and LSD. In May 2018, the DEA issued an internal directive which reads, "Products and materials that are made from the cannabis plant and which fall outside the CSA [Controlled Substance Act] definition of marijuana (such as sterilized seeds, oil or cake made from the seeds, and mature stalks) are not controlled under the CSA. Such products may accordingly be sold and otherwise distributed throughout the United States without restriction under the CSA or its implementing regulations, …The mere presence of cannabinoids is not itself dispositive as to whether a substance is within the scope of the CSA; the dispositive question is whether the substance falls within the CSA definition of marijuana." But the law still hasn’t changed. Congress has tried and is currently trying to pass bills to remove CBD from the Controlled Substances Act.

Despite the many positive medical applications of CBD, pharmaceutical companies can’t patent a CBD product unless they turn it into a synthetic chemical first. There is one drug whose active ingredient is CBD that has been approved by the US Food and Drug Administration. Epidiolex, made by GW Pharmaceuticals, a British company, was approved in April 2018 by the FDA for use with epilepsy.

CBD oil from hemp is different than hemp oil

CBD products typically come as pills/capsules, as oils with droppers for oral ingestion, sprays and tinctures for absorption in the mouth, and as vaping oil. CBD creams, gels, and lotions are also available for external application to address muscle and joint pain. CBD is non-addictive and can’t be overdosed. It can be ingested safely, although at high doses it can cause gastrointestinal issues and affect certain medications.

When looking to buy CBD oil, pay attention to detail. Just because something is made from hemp doesn’t mean it contains CBD. If “CBD oil” is typed into an internet search box, many hemp oil products will show up. Hemp oil is typically made from hemp seeds, CBD oil from hemp is made from the flowers, leaves, and to a minor extent, the stalk. Hemp seed oil contains minimally low CBD content. Pay attention to CBD content per serving, the amount of CBD and cost per dose can vary widely by product and brand. If the product only lists “cannabinoids” be cautious, the amount of CBD is unknown.

Also be aware that in 2015 and 2016, the FDA issued warning letters because the products did not have the level of CBD as claimed. Warning Letters and Test Results for Cannabidiol-Related Products Some were higher, but most were lower. ConsumerLab.com, an independent laboratory which tests numerous products, also tested some of the more popular CBD products. They also found differences between labels and actual CBD content. They also tested for lead, cadmium, and arsenic contamination and analyzed for cost. Some information is available at ConsumerLab.com, but there’s a fee to obtain the actual product test results. When researching products look for emphasis on quality control, farming practices, and third party testing for product homogeneity, cannabinoid quantitation, and screening for potential harmful contaminants.

CBD oil products are sold with recommended dosages, but experimentation is often best to determine the amount required for an individual’s desired effect. Recommended product dosages are typically low. The dosages in most clinical trials were high, 200 mg or more a day.

Lastly, just because a product contains CBD doesn’t mean the body can use it. See discussion on bioavailability below.

Endocannabinoids

The cannabinoids produced in the body (endo means internal, from within). This occurs naturally in all mammals, without introduction of phtyocannabinoids from cannabis. Phytocannabinoids are a similar in chemical structure to our own endocannabinoids.

Endocannabinoid system (ECS)

A complex signaling network in the human body that uses cannabinoids to control various bodily processes by interacting with different receptors and regulatory enzymes. Most of our knowledge of the ECS is fairly recent, starting in the 1980s. The ECS has two receptors for cannabinoids: CB1 receptors and CB2 receptors.

THC and CBD affect the endocannabinoid system in different ways

CB1 receptors are found all around the body in the nervous system and nerves, but mostly in the brain. CB1 receptors in the brain deal with coordination and movement, pain, emotions and mood, thinking, appetite, and memories, among others. THC attaches mostly to CB1 receptors

CB2 receptors are mostly found in the immune system, effecting inflammation and pain. It used to be thought that CBD acts on these CB2 receptors, but it appears now that CBD does not act on either receptor directly. Instead, it seems to influence the body to use more of its own cannabinoids. CBD actually has a very low affinity for both CB1 and CB2 receptors but acts as an indirect antagonist of their agonists. If CBD did attach to CB1 and CB2 receptors it would have the same addictive potential of THC. But since its mechanism of action is not dependent on receptors associated with addiction, CBD is not addictive or habit-forming.

Bioavailability

Bioavailability is the proportion of a drug or substance that enters the circulation when introduced into the body and so it is able to have its intended effect. CBD is not water soluble, but the body is over 60% water. It's like trying to wash an oily pot with just water, the oil is hydrophobic, it doesn't want to mix with the water, it wants to repel it. Getting any oil based substance to pass through a cell wall is challenging, requiring a higher dose for adequate absorption.

Some products offer “liposomal delivery.” According to What is a Liposome, "A liposome is a tiny bubble (vesicle), made out of the same material as a cell membrane. Liposomes can be filled with drugs, and used to deliver drugs for cancer and other diseases." Lipsomes can be absorbed very quickly through a cell wall, so either in a topical or ingested format, they enhance the effects of CBD and other cannabinoids.

According to popular fitness expert and blogger Ben Greenfield in the article Get all the Health Benefits of Smoking Weed without actually Smoking Weed cannabinoids that are processed into nanoparticle size (1/100 the width of a human hair) are easier for your body to absorb and transport to where they are needed within your body.

In the same article, Ben Greenfield also cites that turmeric (curcumin) aids bioavailability, “…when the cannabinoids and terpenoids in CBD are mixed with the isolated curcuminoids of a high-curcumin containing turmeric plant, the bioavailability of the CBD absolutely explodes. This means that if you’ve used CBD oil before in the absence of a curcuminoid blend from turmeric, you probably only felt about 1/5 to 1/10 of the actual effects of the CBD, since CBD by itself is very poorly absorbed.”

Absorption also depends on the method of administration.

When consumed orally, a cannabinoid has to be processed by the liver and other digestive organs first. Only a percentage passes through these organs and makes it into the bloodstream so it can be used by the endocannabinoid system. If there is excess CBD, it is stored in fat cells and can remain there for days, released gradually for use by the endocannabinoid system. So, although oral consumption doesn’t provide the highest availability, if enough is consumed consistently, oral consumption is an effective way to treat certain conditions.

Oral mucosal administration offers a faster response as it bypasses the digestive system. With this form, a mouth spray or tincture is held under the tongue for 30-60 seconds before swallowing.

Vaping is vapor that is infused with a substance for the purpose of being inhaled to your lungs. Vaporizing allows CBD to be absorbed by the lungs, into the blood, and across the blood-brain barrier. Compared to oral administration, vaping allows nearly three times as much CBD to enter blood circulation and is best for treating symptoms that need to be addressed quickly. The effects of vaping wear off after 2-3 hours.