cannabis medicines

Today there are many cannabis-based products available, from whole-plant formulations, available at medical dispensaries, to completely man-made synthetic drugs that are FDA approved.

Some of these synthetic cannabinoids mimic classic cannabinoids like THC, while others simply activate and modulate the endocannabinoid system in their own unique way, producing somewhat similar benefits to the cannabis plant.1,2

However, there exists a darker side to these synthetic cannabinoids that carry risks far greater than the cannabis plant could ever pose, and it is important to understand the differences.

The Good, the Bad & the Ugly – Exploring the Light & Dark Side of Synthetic Cannabis:

  • The Good – These are drugs that have been safely tested and are still prescribed and used today to treat a variety of diseases and ailments.
  • The Bad – Drugs that failed clinical testing and/or caused disastrous consequences, resulting in their recall.
  • The Ugly – Non-pharmaceutical, non-FDA approved synthetic cannabinoid-like compounds that behave nothing like cannabis in the brain and body. Many of these compounds can be dangerous with severe side-effects.

The Good: Rx Cannabinoid Medications Used Today

good cannabis

Synthetic cannabinoids have been created to abide by the single molecule dogma of pharmacology. This is largely the reason why synthetic cannabinoids have been approved by the FDA rather than full-spectrum, whole-plant therapy; they conform to a model that’s stable and understood (and, of course, patentable).

While access to whole-plant medical cannabis expands across the country, a variety of cannabinoid medicines currently exist and can be found in pharmacies.

Some include pure cannabinoid isolates, man-made synthetic cannabinoids that mirror the structure and function of phytocannabinoids, and man-made synthetic cannabinoids that produce powerful antiemetic effects for cancer patients undergoing chemotherapy, often when other drugs fail.1,2,5,6 

Dronabinol (Marinol)

Dronabinol, sold under the market names of Marinol and Syndros, is synthetic Δ⁹-THC. Approved by the FDA, this synthetic cannabinoid is generally only used to treat chemotherapy-induced nausea and vomiting.5

Although it is arguably not as efficacious as whole-plant therapy, the benefits in certain medical settings (cancer, sleep apnea) landed this synthesized THC drug a Schedule II classification from the DEA.

It is still in use today and can provide relief from the side effects of cancer treatment.

Nabilone

Nabilone, or Cesamet, is a synthetic that mimics THC – it is similar enough in structure to have some positive effects, but it is not THC or any other known cannabinoid.

While it too is used to treat nausea and vomiting for those undergoing chemotherapy, it is also administered for the treatment of movement disorders such as Parkinson’s, chronic pain, multiple sclerosis, and dystonia.1,5,7–10

It has even been used to treat nightmares occurring due to PTSD.11 Nabilone has a slower onset for its peak and a greater dose-dependence of effects, characteristics that were attributed to greater bioavailability.12

The Bad: Once Hopeful Rx Synthetics Turned Disastrous & Deadly

bad cannabis

These compounds were meant for FDA approval until unanticipated side effects and adverse events abruptly terminated their existence.

Getting new drugs to market certainly isn’t easy, and the reality is that most drugs don’t even make it past animal testing, much less all the way to testing in human, clinical trials.

The FDA has a strict and rigorous review process, for good reason. Nevertheless, sometimes potentially dangerous drugs slip through the cracks during clinical trials, and some even end up on the shelves before their harmful nature is realized.

Rimonabant and Other CB1 Blockers

It’s common knowledge that cannabis stimulates appetite, a side effect endearingly dubbed the “munchies.” Science has now found direct links to our own endocannabinoids and their modulation of leptin levels, a hormone made primarily by fat cells (adipocytes) that stimulates hunger.13

Naturally, synthetic chemists and drug manufacturers were extremely hopeful that blocking THC’s partial agonism at CB1 (responsible for the appetite-stimulating properties of the endocannabinoid system) would suppress appetite and help obese patients lose weight.

Unfortunately, the involvement of CB1 in human physiology extends far beyond simply controlling appetite and metabolism; the regulation of mood is another major factor affected.9

The first CB1 blocker created for obese patients was a globally acting synthetic CB1 inverse agonist called Rimonabant. Patients taking Rimonabant indicated a decrease in hunger, but also an alarming (almost two-fold) increase in anxiety, depression and suicidal ideation.14,15

As such, global blockage of CB1 did more than just suppress appetite; it caused psychiatric side effects so severe that the development of CB1 blockers as promising anti-obesity targets came to a screeching halt.16

Unfortunately, we currently don’t fully understand the endocannabinoid system, and this reductionist approach to biology simply isn’t the whole picture.

“Cannabinoid-Based” FAAH Inhibitor Causes Unprecedented Tragedy: Brain Death & Fatality

In the early days of 2016, several news outlets, including the New York Times, the Guardian, and the Independent, reported tragic outcomes for six patients undergoing clinical trials investigating a new cannabinoid-based painkiller in France.16–18

The drug, undergoing a Phase 1 trial, was administered with the hope that it would help with mood, anxiety, and motor problems due to neurodegenerative disease.

It targeted the endocannabinoid system, having been tested on animals before being administered to 90 people.

Six healthy men became ill and were hospitalized shortly after the trial began, suffering potentially irreversible brain damage. One was pronounced braindead.

Early reporting falsely claimed the drug was “cannabis-derived” and/or “contained cannabinoids,” neither of which were ostensibly true, being categorically denied by French’s health minister.

Still, despite following all the regulations, our lack of understanding concerning the endocannabinoid system resulted in the drug being halted.

The Ugly: Black Market Synthetics Deceptively Marketed as “Legal Weed”

ugly cannabis

These dangerous products generally give a bad name to synthetic drugs, tarnish the reputation of cannabis, and color the perception of medically approved products.

These compounds are rogue synthetics made by clandestine laboratories for recreational use/abuse that act nothing like cannabis, while also carrying extreme risks and hazards to one's health, which cannabis, and its FDA approved synthetics, do not.

Yet, due to the federally restrictive scheduling of cannabis as a Schedule I drug, laboratories consistently manufacture and distribute synthetic cannabinoids that often have similar chemical structures but present very different pharmacological and physiological effects for the user.17

Spice and K2

“Spice,” which attempts to mimic cannabinoid compounds, is implicitly marketed as a “legal high,” making its consumption more alluring to people who believe that they can experience the high from cannabis while circumventing legal and career requirements, such as drug testing.14 

These “research chemicals” are often labeled with “JWH” prefixes, such as JWH-018, -007, -005, etc., and are often chemically sprayed onto a combustible, then sold.

K2 is another brand name of a chemical in the same family, and these research chemicals are able to circumvent federal regulations and DEA control due to their analogous, yet non-identical, structure to the federally restricted cannabis plant and its respective cannabinoids.6

In general, the market for research chemicals, also known as “designer drugs,” is growing at a rapid and unprecedented rate; unfortunately, little is known about the majority of these compounds and their potential adverse effects.19

Needless to say, the labs producing synthetic cannabinoids aren’t overly concerned with testing their product or quality control – they’re only concerned with their bottom line.

Even more alarming are these chemical’s effects on one’s mental health. While certain types of cannabis have been shown to potentially cause psychosis in people with underlying mental illness, drugs like K2 and Spice have been shown to cause full-blown psychosis in otherwise healthy people.20, 21

The rates of synthetic cannabinoid use/abuse are rising, and many are undoubtedly still under the presumption that such products are just as harmless as cannabis itself.

The Negative Impact of The Ugly on The MMJ Movement & Public Perception of Cannabis

While there are many synthetic, FDA-approved cannabinoids on the market, it is clear that there is a dark side to synthetic cannabinoids. Tying this toxic family of synthetic chemicals to Cannabis Sativa and the host of efficacious synthetic compounds it has inspired is a grave mistake. It has tarnished the reputation of otherwise effective and safe pharmaceutical medicines.

While legislators struggle to keep up with the production of new synthetic compounds designed to avert the law, it is necessary for the public to be aware and skeptical of such drugs, as they are often not what they claim to be.

Selling plant matter sprayed with chemical cannabinoids that have undergone no testing, interact with the brain and body in ways completely distinct from Cannabis Sativa, and that have dangerous, even lethal effects, is a deviant affront to the progress made by an otherwise compassionate community of cannabis patients and advocates.

Cannabinoid Medicine as Mainstream Medicine

While we may still be discouraged by the persistent classification of Cannabis Sativa, a unique integration of cannabis and modern medicine should pave the way for a better understanding of how these compounds can help us, hopefully resulting in a more educated, tolerant, and discerning populace, at least in terms of cannabis.

The medical cannabis movement continues to be patient driven, priding itself on helping patients break free from the chains of chemical dependency and addiction, as states with cannabis pilot programs show lower opioid-related overdoses and deaths in Medicare part D patients.4

If whole-plant therapy is not a viable, legal option, it is important to stay informed of the available options and steer clear of synthetics that may cause more harm than good.


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Works Cited

1. Ware1, M. A., Daeninck, P. & Maida, V. A review of nabilone in the treatment of chemotherapy-induced nausea and vomiting. Ther. Clin. Risk Manag. 4, 99–107 (2008).

2. May, M. B. & Glode, A. E. Dronabinol for chemotherapy-induced nausea and vomiting unresponsive to antiemetics. Cancer Manag. Res. 8, 49–55 (2016).

3. Wehrman, J. Fake marijuana spurs more than 2,500 calls to U.S. poison centers this year alone. Am. Assoc. Poison Control Cent. (2010).

4. Bradford, A. C. & Bradford, W. D. Medical Marijuana Laws Reduce Prescription Medication Use In Medicare Part D. Health Aff. Proj. Hope 35, 1230–1236 (2016).

5. Badowski, M. E. A review of oral cannabinoids and medical marijuana for the treatment of chemotherapy-induced nausea and vomiting: a focus on pharmacokinetic variability and pharmacodynamics. Cancer Chemother. Pharmacol. 80, 441–449 (2017).

6. Press Announcements > FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy. Available at: https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm611046.htm. (Accessed: 8th February 2019)

7. Parker, L. A., Rock, E. M. & Limebeer, C. L. Regulation of nausea and vomiting by cannabinoids. Br. J. Pharmacol. 163, 1411–1422 (2011).

8. Cannabinoids remove plaque-forming Alzheimer’s proteins from brain cells. Salk Institute for Biological Studies

9. Cannabidiol to Improve Mobility in People with Multiple Sclerosis. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874292/. (Accessed: 6th February 2019)

10. Fanelli, G. et al. Cannabis and intractable chronic pain: an explorative retrospective analysis of Italian cohort of 614 patients. J. Pain Res. 10, 1217–1224 (2017).

11. Morgenthaler, T. I. et al. Position Paper for the Treatment of Nightmare Disorder in Adults: An American Academy of Sleep Medicine Position Paper. J. Clin. Sleep Med. JCSM Off. Publ. Am. Acad. Sleep Med. 14, 1041–1055 (2018).

12. Subjective, cognitive, and cardiovascular dose-effect profile of nabilone and dronabinol in marijuana smokers. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335956/. (Accessed: 8th February 2019)

13. Leptin-regulated endocannabinoids are involved in maintaining food intake. - PubMed - NCBI. Available at: https://www.ncbi.nlm.nih.gov/pubmed/11298451. (Accessed: 11th February 2019)

14. Kunos, G. & Tam, J. The case for peripheral CB1 receptor blockade in the treatment of visceral obesity and its cardiometabolic complications. Br. J. Pharmacol. 163, 1423–1431 (2011).

15. Tam, J. et al. Peripheral CB1 cannabinoid receptor blockade improves cardiometabolic risk in mouse models of obesity. J. Clin. Invest. 120, 2953–2966 (2010).

16. 6 Hospitalized, One of Them Brain-Dead, After Drug Trial in France - The New York Times. Available at: https://www.nytimes.com/2016/01/16/world/europe/french-drug-trial-hospitalization.html. (Accessed: 11th February 2019)

17. French drug trial leaves one brain dead and five critically ill | Science | The Guardian. Available at: https://www.theguardian.com/world/2016/jan/15/french-drug-trial-one-person-in-coma-and-five-critically-ill. (Accessed: 11th February 2019)

18. France clinical trial: One person brain-dead and five in hospital after drug testing ‘accident’ in Rennes | The Independent. Available at: https://www.independent.co.uk/news/world/europe/france-clinical-trial-one-person-brain-dead-and-five-more-in-hospital-after-drug-testing-a6813791.html. (Accessed: 11th February 2019)

19. Choo, E. K., Feldstein Ewing, S. W. & Lovejoy, T. I. Opioids Out, Cannabis In: Negotiating the Unknowns in Patient Care for Chronic Pain. Jama 316, 1763–1764 (2016).

20. Wilson, N. & Cadet, J. L. COMORBID MOOD, PSYCHOSIS, AND MARIJUANA ABUSE DISORDERS: A THEORECTICAL REVIEW. J. Addict. Dis. 28, 309–319 (2009).

21. Roberto, A. J. et al. First-Episode of Synthetic Cannabinoid-Induced Psychosis in a Young Adult, Successfully Managed with Hospitalization and Risperidone. Case Rep. Psychiatry 2016, (2016).