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Do Marijuana or CBD Make Real Medicine?
A USC pharmacologist probes the potential of a controversial plant

03/21/2019 By James David Adams Jr., Ph.D., USC, with an addendum by Craig Weatherby

Today's guest article is by James David Adams Jr., Associate Professor of Pharmacology
in the University of Southern California (USC) School of Pharmacy. Dr. Adams is an expert in medicinal plants, human drug metabolism, herbal remedies, antioxidants, and drugs for treatment of stroke. It comes to us courtesy of The Conversation.

A note from the author
“I am a professor in the University of Southern California School of Pharmacy. I've long lived in California and remember the Haight-Ashbury Summer of Love. While in graduate school, I worked with professor Alexander Shulgin, the father of designer drugs, who taught me the chemistry of medicinal plants.”

“Afterwards, while a professor at USC, I learned Chumash healing from a Native American Chumash healer for 14 years from 1998 until 2012. She taught me how to make medicines from Californian plants, but not marijuana, which is not native to the U.S. Currently, I am teaching a course in medical marijuana to pharmacy students.”

Editor's note: Scroll or click to the bottom of this article to read our addendum about the effects of CBD on pain, and about the opposing influences of dietary omega-3 and omega-6 fatty acids on the human endocannabinoid system's effects on pain and weight gain.


MARIJUANA IS A LOT MORE THAN JUST THC
A pharmacologist looks at the untapped healing compounds

By James David Adams Jr., Ph.D., University of Southern California

Medical marijuana is legal in 33 states as of November 2018. Yet the federal government still insists marijuana has no legal use and is easy to abuse. In the meantime, medical marijuana dispensaries have an increasing array of products available for pain, anxiety, sex and more.

The glass counters and their jars of products in the dispensary resemble an 18th century pharmacy. Many strains for sale have evocative and magical names like Blue Dream, Bubba Kush and Chocolope.

But what does it all mean? Are there really differences in the medical qualities of the various strains? Or, are the different strains with the fanciful names all just advertising gimmicks?

If there is one thing about marijuana that is certain: In small doses it can boost libido in men and women, leading to more sex. But can marijuana really be used for medical conditions?

What are cannabinoids?
New research is revealing that marijuana is more than just a source of cannabinoids — chemicals that may bind to cannabinoid receptors in our brains, which are used to get high. The most well-known is tetrahydrocannabinol (THC).

Marijuana is also a rich source of medicinal compounds that we've only begun to explore. In order to harness the full potential of the compounds in this plant, society needs to overcome misconceptions about marijuana and look at what research clearly says about the medical value.

The FDA has already made some moves in this direction by approving prescription drugs that come from marijuana including dronabinol, nabilone, nabiximols and cannabidiol.

  • Dronabinol and nabilone are cannabinoids that are used for nausea.
  • Nabiximols — which contain THC, the compound most responsible for marijuana’s high and cannabidiol, which does not induce a high — are used to treat multiple sclerosis.
  • Cannabidiol, or CBD, is also used to treat some types of epilepsy.

Marijuana, originally from the Altai Mountains in Central and East Asia, contains at least 85 cannabinoids and 27 terpenes, fragrant oils that are produced by many herbs and flowers that may be active, drug-like compounds.

THC: The cannabinoid that makes people feel "high"
THC is the cannabinoid everyone wants in order to get high. It is produced from THC acid — which constitutes up to 25 percent of the plant’s dry weight — by smoking or baking any part of the marijuana plant.

THC mimics a naturally occurring neurotransmitter called anandamide that works as a signaling molecule in the brain. Anandamide attaches to proteins in the brain called cannabinoid receptors, which then send signals related to pleasure, memory, thinking, perception and coordination, to name a few. THC works by hijacking these natural cannabinoid receptors, triggering a profound high.

Tetrahydrocannabivarinic acid, another cannabinoid, can constitute up to 10 percent of marijuana's dry weight. It is converted to another compound, tetrahydrocannabivarin, that probably contributes to a high when marijuana is smoked or ingested in baked goods. Potent marijuana varieties like Doug’s Varin and Tangie may contain even higher concentrations.

Medical properties of marijuana
Not all cannabinoids make you high. Cannabidiol, a cannabinoid similar to THC, and its acid are also present in marijuana, especially in certain varieties. But these do not cause euphoria.

The cannabidiol molecule interacts with a variety of receptors — including cannabinoid and serotonin receptors and transient receptor potential cation channels (TRP) — to reduce seizures, combat anxiety and produce other effects.

Marijuana also contains several monoterpenoids — small, aromatic molecules — that have a wide range of activities including pain and anxiety relief and that work by inhibiting TRP channels.

Myrcene is the most abundant monoterpenoid, a type or terpene, in marijuana. It can relax muscles. Other terpenes such as pinene, linalool (also found in relaxing lavender), limonene and the sesquiterpene, beta-caryophyllene are pain relievers, especially when applied directly to the skin as a liniment. Some of these terpenes may add to the high when marijuana is smoked.

What do all these varieties do?
Many different varieties of marijuana are on the market and are alleged to treat a range of diseases. The FDA has no oversight for these claims, since the FDA does not recognize marijuana as a legal product.

Strains of marijuana are grown that produce more THC than cannabidiol or vice versa. Other varieties have abundant monoterpenoids.

How do you know that the strain you choose is legitimate with probable medical benefits? Each strain should have a certificate of analysis that shows you how much of each active compound is present in the product you buy.

Many states have a bureau of cannabis control that verifies these certificates of analysis. However, many certificates of analysis do not show the monoterpenoids present in the marijuana. The analysis of monoterpenoids is difficult since they evaporate from the plant material. If you are looking for a strain high in myrcene or linalool, ask for proof.

Researchers have also shown that anxiety can be effectively treated with strains that have more cannabidiol and linalool. It may be best to rub a cannabidiol balm or lotion on your cheeks to relieve anxiety.

Other conditions that studies have shown are improved by marijuana are: cancer-induced nausea, Type 2 diabetes, two forms of epilepsy, HIV-induced weight gain, irritable bowel syndrome, migraines, multiple sclerosis, osteoarthritis, rheumatoid arthritis, pain, chronic pain, post-traumatic stress disorder, sleep disorders and traumatic brain injury.

For some of these conditions, studies show that eating or topically applying marijuana products rather than smoking is recommended.

Clearly, more research is needed from the scientific community to help guide the appropriate, safe use of marijuana. However, the FDA does not recognize the use of medical marijuana.

This makes funding for research on marijuana difficult to find. Perhaps the cannabis industry should consider funding scientific research on marijuana. But conflicts of interest may become a concern as we have seen with drug company-sponsored studies.

Potential adverse side effects
Marijuana can improve several conditions, but it can also make others worse and can have nasty side effects.

As recreational use has become more widespread, marijuana hyperemesis [cyclical vomiting] syndrome is becoming more of a problem. Some people vomit uncontrollably after smoking marijuana regularly. It can be treated by rubbing a cream made from capsaicin, from chili peppers, on the abdomen. Capsaicin cream is available in pharmacies.  [Editor's note: Hot-water baths also appear to help some sufferers, but the surest, if not certain, remedy is to stop consuming marijuana.]

Also, high THC varieties of marijuana, such as Royal Gorilla and Fat Banana, can cause anxiety and even psychosis in some people.

Editor's note: You can view Dr. Adams' original article here.


Addendum to Dr. Adams' article, by Craig Weatherby

About CBD and pain: The clinical evidence is thin and mixed

As professor Adams noted, the marijuana variety of cannabis contains monoterpenoid compounds that appear to provide some pain relief.

But virtually all the focus on the pain-relief potential of marijuana and hemp has been on CBD.

Some retail stores (in states that permit the sale of marijuana) carry CBD products such as topical ointments, edible liquid extracts, sprays, and chewable/edible “gummies” — which are typically purchased to alleviate pain or anxiety or to aid sleep.

But what is the evidence that topical or oral CBD can alleviate significant pain?

The answer matters a great deal, because at today’s prices, the effective oral dose for temporary pain relief — which ranges from 800 mg to 1,500 mg — is extremely costly, at $50-$70 in Massachusetts, for example. (The wholesale price of hemp — which is the source of commercial CBD — has been dropping, as should the retail cost of CBD.)

Unfortunately, it’s not yet clear whether or to what extent oral CBD can provide significant pain relief. The several evidence reviews published in recent years have come to varying conclusions, but none have found strong, unambiguous evidence that oral CBD can consistently provide significant pain relief.

That said, there are enough positive indications from the clinical studies covered by these reviews that it’s reasonable for someone with internal pain (such as joint pain) to try oral CBD, recognizing that a single effective (i.e., 1,000mg) oral dose can be quite costly.

There is much less evidence regarding the efficacy of topical CBD or whole cannabis, but there is an ancient folk history of using topical cannabis for pain relief — and there are some encouraging preliminary indications from rodent studies and at least one human clinical report (Maida V, Corban J 2017).

As the Canadian authors of that case-studies report wrote, “Extracts derived from the cannabis plant have been applied to wounds for thousands of years. We are reporting a prospective case series of three patients with pyoderma gangrenosum [surface ulcers] that were treated with topical medical cannabis ... Clinically significant analgesia [pain relief] that was [also] associated with reduced opioid utilization was noted in all three cases. Topical medical cannabis has the potential to improve pain management in patients suffering from wounds of all classes.”

America's "omega imbalance" promotes pain and weight gain, via its malign effects on the body's own cannabinoid compounds

The body’s internal cannabinoids — known as endocannabinoids — help regulate nerve/brain inflammation and inflammatory pain signals, as well as appetite and for “working” memory.

The endocannabinoid system or ECS also plays key roles in brain remodeling in response to stimuli and in the growth of brain cells and connections between them.

In recent years, British researchers reported that long-term consumption of omega-3s (DHA and EPA) from seafood or fish oil reduces the levels of certain endocannabinoids (anandamide compounds) associated with overeating and replaces them with analogous but beneficial endocannabinoid-like DHA- and EPA-derived molecules (Dally SC et al. 2016; Dally SC 2017).

And last year, Brazilian researchers underscored two important points (Freitas HR et al. 2018):

  • "Today, the ECS is known to be involved in diverse functions such as appetite control, food intake, energy balance, neuroprotection, neurodegenerative diseases, stroke, mood disorders, emesis, modulation of pain, inflammatory responses, as well as in cancer therapy."
  • "Western diet[s] as well as restriction [lack] of micronutrients and fatty acids, such as [omega-3] DHA, could be related to altered production of pro-inflammatory mediators (e.g. eicosanoids) and ECs, contributing to the progression of cardiovascular diseases, diabetes, obesity, depression, or [mentally] impairing conditions such as Alzheimer' s disease." (Freitas HR et al. 2018)

Unfortunately, the extreme overload of omega-6 fats and serious shortage of omega-3 fats in the standard American diet affects the endocannabinoid system in ways that tend to promote pain, inflammation, and weight gain.

We reported on studies documenting these effects in two articles: Krill Oil Kills the Munchies in Mice and America's Hidden Pain & Weight Problem.

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