Synchronicity in Whole Plant Medicine

By Owen Smith

Abbreviations: D9-THC, D9-tetrahydrocannabinol; D8-THC, D8-tetrahydrocannabinol; CBN, cannabinol; CBD, cannabidiol; D9-THCV, D9-tetrahydrocannabivarin; CBC, cannabichromene; CBG, cannabigerol; D9-THCA, D9-tetrahydrocannabinolic acid; CBDA, cannabidiolic acid; TRPV1, transient receptor potential vanilloid type 1; PPARg, peroxisome proliferator-activated receptor g; ROS, reactive oxygen species; 5-HT1A, 5-hydroxytryptamine receptor subtype 1A; FAAH, fatty acid amide hydrolase.(+), direct or indirect activation; “, increase; #, decrease.

In the last article I discussed how the flowers, stalk, and leaves of the cannabis plant can be used to create a range of edible medical products that offer stimulation for the daytime, and sedation for at night. I began to explore the role of cannabidiol (CBD) in the treatment of many serious medical conditions and in relation to tetrahydrocannabinol (THC) in whole plant cannabis. Also, the synthetic THC pills were discussed, as presently pharmaceutical companies develop synthetic CBD compounds for a wide range of conditions (see Figure 1). As patients in pain lose patience with prohibition, scientists in labs are opening the Pandora’s Box of whole plant cannabis, confirming its important role in understanding human health.

To better understand the complexities of cannabis and our health we need to learn about our endocannabinoid system (ECS). “Endocannabinoids are lipid compounds produced in our bodies by burning and making fats.”1 These compounds are like keys that fit into neurotransmitter receptor sites, widely distributed throughout our bodies, like specific locks. When a key (ex. 2-AG) binds with a lock (ex. CB1) the site is activated. These ECS receptor sites are activated by synthetic and plant derived phytocannabinoids, as well as by the internally generated endocannabinoids. For example there is a compound produced in the body that is identical to THC called anandamide (AEA) or “bliss within.” “These ‘endocannabinoids’ are released onto their receptors in a manner that appears to maintain homeostasis within the central nervous system.”2 The two kinds of endocannabinoid receptor sites are termed CB1 and CB2. CB1 is one of the most ubiquitous neurotransmitters in the human body and is primarily found in the nervous system while CB2 is predominantly found in the lymphatic system.

The discovery of the built in ECS is helping to explain the complex entourage of effects produced by whole plant cannabis. Phyto and endo cannabinoids work together to activate the CB1 and CB2 receptor sites. The entry on Apr. 20, 2011, explains how “CBD indirectly stimulates the production of anandamide by suppressing the enzyme fatty acid amide hydroxylase (FAAH). FAAH is responsible for breaking down anandamide, less FAAH means more anandamide remains present in the body for a longer duration. More anandamide means greater CB1 activation. CBD also stimulates the release of 2-AG, another endocannabinoid that activates both CB1 and CB2 receptors.”3

Cannabinoid receptors represent an exciting new target for medical research, yet only confirm what patients have been saying for decades. Seriously ill people who have run the gamut of conventional medicine to no effect, and have sought to use cannabis through their doctor, have often been prescribed Marinol or Cesamet—the synthetic THC cannabis pills. The THC pills have been used by doctors as a third tier medication, citing a shortage of studies and assuming the limited therapeutic value of cannabis by default. Many doctors who have stayed in the closet about cannabis are only now learning from patients about the effectiveness of whole plant cannabis medicines made by dispensaries. Whole plant cannabis products have distinctive advantages over isolated cannabinoid drugs. In the book Marihuana: The Forbidden Medicine, doctors Lester Grinspoon and James Bakalar found that “whole cannabis causes fewer psychological side effects than synthetic THC, seen as symptoms of dysphoria, depersonalization, anxiety, panic reactions and paranoia.”4

One of the most important distinctions between synthetic THC and whole plant cannabis is the presence of CBD. “CBD antagonizes THC and competes with THC to fill the cannabinoid receptor site.”5 Drug companies are patenting cannabinoids like CBD as non-psychoactive medications for many conditions. A recently published study in Nature Neuroscience found that a CBD derivative “JWH133, a synthetic drug that activates the CB2 receptor, reduced intravenous cocaine administration in mice by 50-60%.”6 This evidence suggests that other than a gateway to drug abuse, cannabis contains compounds that terminate seriously addictive behaviour. JWH133 is currently available online in wholesale for around $5000 a Kilo.7

Canadian companies IntelGenX and Cynapsus (formerly Cannasat) are now developing a synthetic CBD drug for market. “Modulyn is a CBD (cannabidiol) derived product that targets the endocannabinoid system to treat mood disorders such as schizophrenia, anxiety, and depression.”8 Modulyn and its synthetic THC accomplice Relivar are delivered by a capsule that melts in the mouth. This provides partial absorption through the oral mucous membrane, quickening the onset of the effects and reducing the amount of drug metabolized by the liver. When swallowed, THC transforms into the metabolite, 11-Hydroxy THC, which is known to be more psychoactive than THC itself yet also “may be necessary for the mediation of analgesic activities.”9 Modulyn and Relivar are part of a focus on new medications for the brain to treat neurological diseases such as Parkinson’s.

Sativex, which is available in Canada by prescription, has a “1:1 dose ratio combination of CBD:THC.”10 Sativex, unlike the aforementioned synthetics, is derived from cannabis plants grown in a laboratory, and is classified as a Botanical Drug Substance. However, Sativex is an alcohol based oromucosal (mouth) spray that has been shown to “cause irritations in the mouth in 20-25% patients in clinical trials.”11 In a comparative study, former VICS owner Phillipe Lucas found that although superior to Marinol and Cesamet, Sativex is inferior to inhaled whole cannabis due to the delay of onset, and concluded that “the high cost (my total for this 5-day trial was 45 sprays, or $135 worth of Sativex) is sure to be prohibitive to many who might otherwise benefit from its use.”12

Last year GW Pharmaceuticals sold the rights to Sativex to a Japanese company. “Otsuka’s willingness to contemplate paying up to a quarter of a billion dollars in royalties and fees for one cannabis-based pharmaceutical with a less than overwhelming efficacy profile indicates that the total market for medical cannabis products is a multi-billion prospect.”13

Figure 1. Pharmacological actions of non-psychotropic cannabinoids (with the indication of the proposed mechanisms of action).14

In American states where dispensaries are licensed, Cannabis Based Medicinal Extracts (CBMEs) are screened for safety by certified third party inspectors like, in Mendocino County. These private laboratories assist dispensaries to ensure that their products maintain high standards. CBDscience LLC has developed three distinct cannabis tinctures: one “High CBD and low THC (4:1 ratio),” one “THC and CBD (1:1 ratio),” and one “high THC and low CBD (20:1 ratio).”15 These organizations are collaborating on “the Great CBD Hunt of 2011,” and working together to collect and cultivate CBD rich strains.

Dispensaries often offer cannabis massage oils and salves extolling their anti-inflammatory, analgesic, and localized health benefits. The ECS is present in the skin and responsible for our natural protection from the drying effects of sun and wind. “It seems that the main physiological function of the cutaneous ECS is to constitutively control the proper and well-balanced proliferation, differentiation and survival, as well as immune competence and/or tolerance, of skin cells.”16 Following the emergence of exciting research including “the recent discovery that topical cannabis preparations can be effective against MRSI, the deadly antibiotic-resistant flesh-eating disease.”17 More interest is forming around the benefits of cannabis for the skin. Members of the CBC of C have reported rapidly healing third degree burns, clearing poison oak, and curing skin cancer.18

In recent years, the whole plant “synergistic shotgun” approach has gained ground over the single ingredient “silver bullet” method. The Aug. 2011 British Journal of Pharmacology: Cannabinoids in Biology and Medicine, Part 1 includes numerous articles exploring the nature of this plant medicines’ dynamism.
In the article “Taming THC,” reports scientists have discovered more than a hundred terpenes that “may contribute meaningfully to the entourage effects of cannabis-based medicinal extracts.”19 The entourage effect of secondary compounds such as terpenes and flavanoids synergize and mitigate the active cannabinoids. The scientist who first isolated the THC compound, Raphael Mechoulam, suggests that “Investigations of the effect of the active component in the presence of its ‘entourage’ compounds may lead to results that differ from those observed with the active component only.”

Cannabis Science Inc. is exploring the possibility that certain terpenes act as building blocks for the production of cannabinoids, with the hope that this will open up to cultivators the opportunity to manipulate cannabinoids to desired ratios. Many plant terpenes act synergistically with other terpenes and some serve to either catalyze or inhibit the formation of other compounds within a plant. Cannabis grown with care and attention to the curing process will contain more terpenes that could play a role similar to CBD in abating the psychoactive side effects of THC.

Anecdotal evidence suggests that the terpene alpha-pinene is alerting, limonene is “sunshine-y,” and beta-myrcene is sedating. As the names suggest, pinene is abundant in pine needles and limonene in lemons. Traditional responses to cannabis overdose include pinene-rich black pepper, limonene-rich citrus, and calamus root high in myrcene. Myrcene is also found in hops (Humulus), the only other member of the Cannabaceae plant family. Ed Rosenthal, author of many books on cannabis, relates that the myrcene in mangos can increase the quality of low potency cannabis when eaten one hour before medicating. “Cannabis terpenoids and flavonoids may also increase cerebral blood flow, enhance cortical activity, kill respiratory pathogens, and provide anti-inflammatory activity.”20

The rabbit hole gets deeper when we consider beta-caryophyllene (BCP), which is another terpene that contributes to the aroma and flavour. Studies show that this terpene, also found in other legal herbs, spices, and food plants, activates the CB2 receptor and acts as a non-psychoactive anti-inflammatory. Because it binds to a cannabinoid receptor […] and since it is an FDA approved food additive and ingested daily with food, it is the first known dietary cannabinoid.21 Leading the way on terpene identification is Green House Seed Company in Holland who have performed spectral analysis of each of their strains and developed a flavour wheel22 identifying 16 different terpenes to help individuals decide on their strain of choice.

In light of this, scientists isolating cannabinoids into synthetic compounds have to consider the terpene interaction as another variable potentially responsible for the plants therapeutic dynamism. Drug companies have been slow to keep up with this field of research, as many terpenes are FDA approved and therefore easy to obtain for testing.
It is becoming increasingly evident that the complex processes and transformations that occur in our bodies are intimately connected to the complex chemistry of the living cannabis plant, and it is through this complex relationship that comes the extensive list of medical treatments.

The symbiotic relationship between our bodies and this plant presents a natural mystery that is confounding the methods of modern medicines makers. The intimacy of the ECS and our health should not be underestimated and, in some cases, tinkered with. Rimonabant was designed to block the CB1 receptor in an attempt to produce the “reverse munchies” effect. It was released in France as an appetite suppressant named Acomplia, only to be rejected shortly after by the U.S. F.D.A. for causing anxiety, depression, and suicidal thoughts.

While drug companies attempt to patent isolated compounds, patients are better off vaporizing whole plant cannabis for fast relief, eating leaf-based medibles for a long sleep, or applying a massage oil to localize the effects. Cannabis dispensaries offer these options to patients at reduced cost, as they buy bulk ingredients and often receive leaf donations from their caring growers.

Although drug company proponents contest that isolated pharmaceuticals are safer than raw herbs, there has been a genesis of designer cannabinoid drugs that have made it onto the shelves of head shops and gas stations around the world. These compounds were formulated by Dr. John W. Huffman (JWH) in order to conduct experiments with CBD on human subjects without the use of plant derived cannabinoids. The research was funded exclusively by the National Institute of Drug Abuse whose narrow focus on “research to prevent and treat drug abuse and addiction”23 callously blocks whole plant medicine. Dr. Huffman reports that the chemical blueprints of his compounds were stolen and are now being reproduced around the world. JWH has stated publicly that these compounds are unsafe, and reports are emerging of users involved in accidents related to its impairment.

“Spice” smoking blends like K-2 are made into “incense” by spraying JWH compounds soaked in acetone (nail polish remover) onto dried herbs like damiana. At about $420 an ounce, these products are labelled “not for human consumption,” yet are marketed as “Legal Weed,” sometimes causing anxiety and dizziness while offering no medical value. These synthetic constructs continue to run amuck, as the specific profile of these duplicate cannabinoids are unclassified by the law. “Many of these cannabinoids have been developed specifically so they’re not analogues of the other ones […] Theoretically there are thousands that could be developed.”24

In light of this, it seems like another backfire of prohibition that synthetic copies of individual compounds originally found in the cannabis plant are being freely and widely distributed. Evidence continues to emerge in favour of whole plant medicine despite the narrowly focussed research approval standards of organizations like the N.I.D.A. that precipitated this legal loophole for opportunistic chemists. Despite the backwards policies of the current era of prohibition, cannabis may have surpassed all other plants in the breadth of its therapeutic value.

Scientists have only been learning about cannabinoid receptors since 1988. The deeper they explore this complex system the more it reveals about cannabis and our health. As patients continue to inform doctors about how cannabis has helped them, scientists arduously attempt to target these previously untreatable conditions. However, today, it seems clear that the synthetic cannabinoid medicines we have available fall short of the miraculous benefits attributed to whole plant products offered by community dispensaries.

While new synthetic cannabis products are tested and approved, the age old herb will continue to help people heal. May the continued vigilance of cannabis activists finally unveil the irrefutable truth that cannabis is indeed greater than the sum of its parts.


1. The Cannabinoid System, Dr. Robert J. Melamede, Ph.D. <>
2. Ligands that target cannabinoid receptors in the brain: from THC to anandamide and beyond. <>
3. Grinspoon and Bakalar, 1997 Marihuana: The Forbidden Medicine
5. NELSON, 2000 Hemp Husbandry
6. Brain cannabinoid CB2 receptors modulate cocaine’s actions in mice <>
8. <>
9. Analgesic properties of the tetrahydrocannabinols, their metabolites, and analogs <www.ncbi.nlm.nihhow do our bodies make>
10. <>
11. Ibid.
12. PharmaCannabis, Lucas 2006 <>
13. <>
14. Chart of the Pharmacological actions of non-psychotropic cannabinoids <>
15. <>
16. The endocannabinoid system of the skin in health and disease: novel perspectives and therapeutic opportunities. <>
17. Ibid.
18. Cannabis Salve, Testimony <>
19. Russo, 2011 Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects <>
20. 2001 McPartland and Russo, Cannabis and Cannabis Extracts: Greater Than the Sum of Their Parts? <>
21. Beta-caryophyllene is a dietary cannabinoid <>
22. <>
23. <>
24. Designer drugs a cat-and-mouse game <>

Owen Smith
Owen has been writing for the Cannabis Digest since 2009, covering a wide range of topics related to medical cannabis. Owen’s articles are closely related to his constitutional challenge to legalized cannabis edibles extracts and oils. He is the founder of Ethical Growth Consulting

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