Cannabinoid Deficiency and Its Impact on Human Health and Disease, Part 4

By Jonn Desnoes, OMD, MD, PhD, Sandra Kischuk, MSMIS, MCPM

Adverse Effects, Drug Interactions, and Contraindications

In reviewing 31 medical marijuana trials, Borgelt, et al noted that researchers reported 4,779 adverse events in patients receiving a medicinal cannabinoid for 8 to 12 months. Of these, 96.6 percent events were not serious (most common: dizziness – 15.5%). There were 164 serious events, the most common being multiple sclerosis relapse (12.8% of the events), vomiting (9.8% of the events), and urinary tract infection (19.1% of the events).¹

Other mild-to-moderate adverse effects included “somnolence, ataxia, blurred vision, headache, dry mouth, sedation, dizziness, conjunctival irritation/dry eyes, hypotension, feeling intoxicated, nausea, and difficulty with concentration and/or memory.” Most of the reported adverse effects are typically not serious, with the most common being dizziness.¹

But, what of the effect of exogenous (outside) cannabinoids on the brain?

A study by Giovanni Battistella, et al investigated brain structure changes in a group that smoked cannabis on a regular basis and a group that smoked it only occasionally. All subjects were between the ages of 19 and 21, had no psychiatric disorders, used only cannabis—no other drugs, and were split into two groups based on age of first cannabis use, in order for the investigative team to evaluate effect of cannabis on the developing brain²:

In normal adolescents the volume of cerebellar gray matter starts to decrease around puberty and continues to do so until early adulthood . . . (probably) due to the pruning of the (unused) synaptic connections . . . (by) endogenous cannabinoids.²

END

This may be the first study showing temporal pole gray matter atrophy in regular cannabis users with the degree of atrophy directly correlated with drug use frequency three months before the study began, as well as medial temporal cortex changes (a common finding associated with cannabis addiction and regular cannabis use). However, another possibility is that abnormal pruning may result from a genetic predisposition: The researchers would have no way of knowing whether the brain changes were present before or were the result of cannabis use.²

This study on the effects of long-term exposure to cannabis on brain structure integrity found the following:

• An association between regular cannabis-reduced gray matter volume in cannabinoid-CB1-receptor-rich regions “functionally linked to motivational, emotional, and affective processing”;

• A correlation between the magnitude of these changes and frequency of cannabis use; and

• The magnitude of these changes was modulated by the age at which an individual started smoking cannabis.²

Of interest is that past studies have shown that the body may be neuroadaptive: Cognitive changes and CB1 activity may become normal after a period of cannabis abstinence. The researchers could not reach a conclusion as to whether the structural changes were permanent or temporary and recommended longitudinal studies.²

One of the things we need to remember is that what we have today “ain’t your mama’s marijuana.” Over the past 40 years, cannabis growers have concentrated on increasing the THC content and reducing CBD because a better “high” meant more money for the grower. CBD steps down the psychoactive effect of THC, which is of no help if you are trying to get high or trying to sell a premium psychoactive product. Since CBD is attracted to both CB1 and CB2 receptors, it may also serve in a protective capacity. THC is close to a perfect fit for the CB1 receptor. CBD (cannabidiol) is not a perfect for either the CB1 or the CB2 receptor; “it stimulates both types of receptors without actually binding to them.”³

Project CBD research has shown that CBD counteracts the psychoactive effects of THC by inhibiting its effects on CB1 receptors. CBD also causes an increased release of 2-AG, one of the endogenous cannabinoids. Like CBD, 2-AG stimulates both CB1 and CB2 receptors, which enhances the overall effect on the body. Studies published by the have shown that cannabidiol also inhibits the activity of fatty acid amide hydroxylase, or FAAH. This slows the deterioration of anandamide,³ the aforementioned “bliss“ endocannabinoid.

Psychiatric Issues

Marijuana’s chief psychoactive component, THC, is an agonist of the CB1 receptors, which function to modulate appetite, mood, and motivation. An individual’s response to marijuana depends on dosage level, the strain of marijuana, and frequency of use. Typically, marijuana will induce “mild euphoria, sedation, relaxation, hunger, and enhanced sensory input.” It will also impair “attention, balance, cognition, judgment, memory, and sense of time.” Some less fortunate users experience “anxiety, disorientation, paranoia, and psychosis.” A higher relative level of cannabidiol may be protective and reduce the frequency of psychotic symptoms.¹

Cannabis use does not cause schizophrenia, but adolescents who use marijuana heavily can have earlier onset of and double the risk of developing this chronic neurodevelopmental disorder. Ongoing use of cannabinoids after the onset of schizophrenia increases psychosis severity, fragments attention, and makes impulse control difficult, if not impossible.¹ Physiologically, cannabis use interferes with adolescent neurodevelopment, with imaging studies showing compromised hippocampus and cerebellum maturation.¹

Cannabis use is associated with memory and cognition impairment; heavy use, in particular, is associated with deficits in the encoding, storage, and retrieval of memory. The latter correlates with the visible brain structure atrophy in memory areas: the amygdala and hippocampus. Typically, executive function, information processing, and visuospatial perception suffer with marijuana use.¹

Researchers have found a modest association between frequent cannabis use and depressive disorders, impulsivity, and suicidal ideation and attempts. And there are concerns about dependence: BLOCK QUOTE

Cannabis is the most commonly used and abused illicit substance in the world. In the United States each year, approximately 6500 individuals begin to use marijuana daily, of whom 10–20% will develop cannabis dependence. Among people admitted to substance treatment facilities in the United States, marijuana is the most frequently identified illicit substance.¹ END

Pediatric Issues

Calls to the National Poison Data Center have increased with the increased availability of medical marijuana. Symptoms of acute cannabinoid toxicity include such neurologic symptoms as “decreased coordination, decreased muscle strength, lethargy, sedation, difficulties concentrating, altered psychomotor activity, slurred speech, and slow reaction time . . . tachycardia, and dry mouth.” Pediatric patients may exhibit more severe symptoms such as apnea and cyanosis. Common symptoms include ataxia, somnolence, lethargy, altered mental status, severe hyperextension, and spasticity. Although no deaths related to marijuana have been reported to national poison centers, there can be significant morbidity.¹

The increased availability of cannabinoids increases the risk for exposure in children and adolescents, which often results from consumption of cannabis-laced foods. This is complicated by the lack of safety or regulatory packaging. Best practice for cannabis products, as for all prescription and over-the-counter drugs, is to always secure drugs in a safe place with child-proof locks.¹

The Entourage Effect

In 1999, Raphael Mechoulam co-authored a paper with Shimon Ben-Shabat, et al, “An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity,” that changed the way cannabis researchers would approach future studies. Mechoulam administered the endocannabinoid 2-AG (2-arachidonoylglycerol) with two related inactive compounds to mice. The result? The 2-AG endocannabinoid bound more easily at the receptors, and the mice exhibited a greater behavioral response than when 2-AG was used alone.⁴

Scientists had searched for years to find the active chemical component in cannabis. What Mechoulam, et al, discovered was that certain compounds, which themselves were biologically inactive, facilitated and enhanced the effect of active components, and that the presence of these inactive constituents could alter the results from those observed when the active component was applied in isolation.⁴ In Mechoulam’s words:

Biologically active natural products, from either plant or animal origin, are in many instances accompanied by chemically related, though biologically inactive, constituents. Very seldom is the biological activity of the active constituent assayed together with the inactive ‘entourage’ compounds. In view of the results described above investigations of the effect of the active component in the presence of its ‘entourage’ compounds may lead to observations of effects closer to those in Nature than investigations with the active component only.⁴ END

In 2001, John McPartland and Ethan Russo published a paper,

“

Cannabis and Cannabis Extracts: Greater Than the Sum of Their Parts?” in the Journal of Cannabis Therapeutics. In this work, they applied the “entourage” concept to the cannabis plant itself, noting “Good evidence shows that secondary compounds in cannabis may enhance the beneficial effects of THC . . . Cannabis terpenoids and flavonoids may also increase cerebral blood flow, enhance cortical activity, kill respiratory pathogens, and provide anti-inflammatory activity.”⁵

A decade later, Russo substantiated the molecular-teamwork hypothesis and expanded on it in a paper published in the British Journal of Pharmacology, “Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects,” which contains an amazing 304 citations.⁶ At a Fall 2010, Israeli-sponsored medical conference, he discussed the role of “minor” phytocannabinoids, including tetrahydrocannabivarin, cannabigerol, and cannabichromene, in synergistically enhancing the therapeutic effects of THC and CBD. His presentation also covered evidence that “phytocannabinoid-terpenoid interactions” enhanced the therapeutic effects of cannabis.⁶

Cannabinoids, themselves, are odorless. Terpenoids, which are made up of repeating 5-carbon molecule chains (isoprene), provide fragrance in aromatic bark and wood, citrus peel, and smelly herbs (eg, sage, mint). Researchers now suspect that these very volatile and very potent terpenoids (of which there are over 200 in cannabis) may have a role to play in providing synergistic support and biofunctional enhancement of cannabinoid benefits. In their 2001 paper, McPartland and Russo had gone so far as to explore the role terpenoids played in expanding the “medicine chest” cannabis provides, detailing the terpenoids that would most augment each of the cannabinoids in practical use.⁵ The addition of terpenoids and flavonoids to the cannabinoid “medicine chest” complicates the genetic development of new strains of cannabis exponentially but impacts the potential for even greater therapeutic results.⁷

Conclusion

A century ago, medical science did not know of the existence of the endocannabinoid system or the role cannabinoids played in the health of the human body. No longer. D Sulak, in his discussion of the endocannabinoid system on the Norml website, dedicated to reforming marijuana law, noted, “The endogenous cannabinoid system, named after the plant that led to its discovery, is perhaps the most important physiologic system involved in establishing and maintaining human health.”⁸ Cannabinoid deficiency has consequences as insidious as any parasitic disease or cancer, laying low and silently destroying health for decades; as consuming as any bacterial or fungal enemy; and as treacherous as any virus hijacking its host’s DNA.

The saddest fact is that the cause of this condition is man-made and politically induced. But, this is nothing new. Even in the 21st century, it is a fact that those who are not medical professionals can be jailed for practicing medicine if they provide advice on health issues, no matter how accurate or helpful. It is also well-known that proponents of alternative medical treatments are often hounded by the government until they willingly stop promoting their ideas, get arrested and incarcerated, or suffer financial destruction through the actions of its agents. Yet, how much of the “conventional” medical care people receive worldwide is dictated by political convenience, powerful individuals with “agendas,” megalithic chemical corporations, and profit-crazed insurance companies? If I were not a medical professional, I could be arrested for recommending or denying appropriate medical treatment. Yet, every day, insurance companies decide what treatments patients can or cannot get. Is this not practicing medicine?

Even the government can decide, not only whether Medicare will or will not cover a procedure, but whether a patient can or cannot get a desired procedure, even if the patient is willing to pay for it out of his or her own pocket. Is it any wonder that in the years 2014 to 2016, Forbes, Time Magazine, WebMD, NBCNews, CBS News, and The Washington Post reported that the United States had the worst, most expensive healthcare in the developed world?

Greed, which stems from illogical, infantile, and irrational fear of privation; obsession with controlling others; and an unbridled hunger for power combined with medical ignorance produced legislation that should never have been enacted. The prohibition of hemp and its related compounds created consequences that have produced needless pain and suffering, unnecessary hardship, and the destruction of the lives of millions of people. The time is long overdue for this criminal act that has been imposed upon humanity to be reversed, and the injustice and needless suffering be brought to an end.

It is time we take a second look at what makes sense and move away from the hysterical “Reefer Madness” mindset. Cannabis has hundreds of chemical components, including some which are exclusive to that plant and that plant alone. We already know of the powerful effect of some of these on treating pain, inflammation, and even cancer. We need to look more closely at everything this plant has to offer and to make it available to those people whose lives it can rebuild and restore. To do anything less is inhumane. To deny hope for a cure is evil.

If we can clarify a complex, emotionally and politically charged subject using unbiased, science-based information; if we can enlighten minds with facts and a new understanding of how the human body works; and if we can demonstrate the wisdom of using a simple God-given plant our bodies were designed to use to restore health; then perhaps we can set in place legislation that is fair and sensitive to peoples’ needs, that does not place profits above human welfare, and that frees people from unnecessary pain and disease.

References

1. Borgelt LM, et al. The Pharmacologic and Clinical Effects of Medical Cannabis. Pharmacotherapy 2013;33(2):195-206.

2. Battistella G, et al. Long-Term Effects of Cannabis on Brain Structure. Neuropsychopharmacology. 2014 Aug; 39(9): 2041–2048.

3. CBD Oil Review. . Accessed Sep 19, 2016.

4. Ben-Shabat S, et al. An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. European Journal of Pharmacology 353 1998 23–31.

5. McPartland J, Russo E. Cannabis and Cannabis Extracts: Greater Than the Sum of Their Parts? Journal of Cannabis Therapeutics. 2001;1(3-4): 103-132.

6. Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol. 2011 Aug; 163(7): 1344–1364.

7. Gardener F. Ethan Russo Reviews the Effects: Terpenoids, minor cannabinoids, contribute to the ‘entourage effect’ of Cannabis-based medicines. O’Shaughnessys: The Journal of Cannabis in Clinical Practice. August 2011.

8. Sulak D. Introduction to the Endocannabinoid System. . Accessed Sep 25, 2016.

Bio

Sir Jonn Desnoes, OMD, MD, PhD, is a physician, who is board certified in homeopathy and Chinese medicine. He is a former nationally syndicated radio talk show host, writer, researcher, athlete, and visionary. He was knighted for his humanitarian work as a medical missionary.

John became interested in the study of cannabis and its health-restoring properties when a friend gave him a bottle of CBD hemp oil. He had suffered with intractable back pain for years as a result of multiple sports injuries incurred over 30 years as an athlete. Within 20 minutes of taking the CBD oil, his excruciating pain stopped. He has found that, as long as he continues to take the oil, he is virtually pain-free.

Dr. Desnoes may be reached by email at . His website is .

Sandra Kischuk, BSBA, MSMIS, MCPM, is a writer, editor, life coach, Toastmaster, and master gardener. Author of Fighting the Dragon: How I Beat Multiple Sclerosis, Sandra’s writing interests include fiction, non-fiction, poetry, scripts, and other people’s résumés. She has written web content for physicians, informational/marketing literature for attorneys, and continuing education courses for dental professionals, and edited professional communications and doctoral theses on subjects as diverse as religion, education, engineering, and psychology.

Additional Reading

Bonnie RJ, Whitebread CH. The Forbidden Fruit and the Tree of Knowledge: An Inquiry into the Legal History of American Marijuana Prohibition. Virginia Law Review. October 1970;56(6).

Brecher, EM and the Editors of Consumer Reports Magazine. The Consumers Union Report on Licit and Illicit Drugs.

The Marihuana Tax Act of 1937: The history of how the Marihuana Tax Act came to be the law of the land. . Accessed Sep 18, 2016.

McPartland M, Guy G. The evolution of Cannabis and coevolution with the cannabinoid receptor – a hypothesis. In Guy, et al, eds: The Medicinal Uses of Cannabinoids; and McPartland JM, et al. Evolutionary origins of the endocannabinoid system. Gene. 2006;370:64-74.

Musto DF. The History of the Marijuana Tax Act of 1937. Arch Gen Psychiat. February 1972;26(2):101-108.

The Report of the National Commission on Marijuana and Drug Abuse. 1972.

Sides, H. Science Seeks to Unlock Marijuana Secrets. National Geographic. June 2015.

The Report of the National Commission on Marijuana and Drug Abuse I. Control of Marihuana, Alcohol and Tobacco.

Whitebread C; USC Law School. The History of the Non-Medical Use of Drugs in the United States. A Speech to the California Judges Association. 1995 California Judges Association Annual Conference.

Authors

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  Jonn Desnoes, OMD, MD, PhD

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  Sandra Kischuk, MSMIS

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