Cannabis (Medical Marijuana) has been used for medicinal purposes for millennia (Please read our previous blog: Introduction to Cannabis and its history of use in medicine.) however, legal use of marijuana ended in 1937 with the passage of the Marijuana Tax Act of 1937. Subsequently, marijuana was classified as a class I drug with no medical benefits. This amazing herb was given the same regulatory classification as cocaine, LSD and heroin. Since 1937 possession and use of marijuana has been against federal law in the United States of America. The legal status of cannabis has evolved over the last 20 or so years. California was the first state to allow the use of medical marijuana with the passage of Proposition 215 in 1996. Currently 29 states (plus Washington DC) allow the use of medical marijuana and 9 states permit the use of recreational marijuana.
History of use of synthetic drugs that affect the Endocannabinoid System (ECS)
Scientific research has uncovered many important properties of the Endocannabinoid System (ECS) and consequently, pharmaceutical companies are attempting to take advantage of the ECS to produce drugs that affect the ECS.
Synthetic THC and Synthetic CBD
The first synthetic ECS modulating drug, Dronabinol (Marinol), was approved by the FDA in 1986. Dronabinol is a synthetic form of tetrahydrocannabinol (THC) and was approved as an appetite stimulant for people with AIDS and as an anti-nausea drug for people experiencing side effects from cancer chemotherapy.
Unfortunately, clinical experience with Dronabinol has been somewhat disappointing. Dronabinol has been found to have a rather narrow “therapeutic window” and many patients experience unpleasant side-effects including drowsiness, dry mouth, rapid heartbeats, lethargy, decreased motor coordination, slurred speech, and dizziness when standing up quickly.
The other disadvantage of Dronabinol is that it takes over one hour for Dronabinol to be effective, whereas smoked or vaporized cannabis can bring relief in seconds or minutes. Additionally many patients using Dronabinol experience acute psychedelic effects. Mark Kleiman, director of the Drug Policy Analysis Program at UCLA’s School of Public Affairs had this to say about Dronabinol, “It wasn’t any fun and made the user feel bad, so it could be approved without any fear that it would penetrate the recreational market, and then used as a club with which to beat back the advocates of whole cannabis as a medicine.”
The next FDA approved cannabinoid drug was Nabilone. Nabilone, which is also a form of synthetic THC, was approved in 2006 as an anti-nausea drug for cancer chemotherapy, and to reduce nerve pain (neuropathic pain).
Unfortunately, patients treated with Nabilone also frequently experience adverse effects including dizziness/vertigo, drowsiness, dry mouth, feeling off balance, sleep disturbances, bad feelings, headaches, nausea, disorientation, and depersonalization. Consequently, Nabilone is not commonly prescribed for its FDA approved uses.
Another synthetic cannabinoid, known as Sativex is a combination of THC and Cannabidiol (CBD) in approximately equal proportions. Sativex was approved for use in the U.K. in 2010 as an oral, sublingual spray, used for muscle spasms resulting from multiple sclerosis. However, Sativex is awaiting FDA approval for use in the United States.
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Cannabinoids not found in Nature – Designer Drugs
Unnatural synthetic cannabinoids are a class of molecules that bind to cannabinoid receptors in the body and are known as “designer drugs”. These dangerous and often illegal substances are typically consumed by smoking and have been marketed as herbal incense, or “herbal smoking blends” and sold under common names like K2, Spice, Synthetic Marijuana, Black Mamba, Bombay Blue, Genie, Zohai, Banana Cream Nuke, Krypton, Lava Red, and many more.
Many synthetic cannabinoids have appeared on the market and are designed in an attempt to avoid the legal restrictions on cannabis, hence the term “designer drugs”.
Most of the synthetic cannabinoids are designed to mimic the effects of THC, leading to psychoactive effects. These cannabinoid mimics can be very powerful as they can bind to cannabinoid receptors more strongly than natural cannabinoids. However, many users of synthetic cannabinoids commonly experience serious, negative effects, including palpitations, paranoia, anxiety, nausea, vomiting, confusion, poor coordination, and seizures. Alarmingly, there have also been reports of compulsive use of these substances, withdrawal symptoms upon stopping these substances and even deaths linked to use of these synthetic cannabinoids.
The legal status of synthetic cannabinoids is complicated because technically each unique cannabinoid analog is new on the market. Nonetheless, some of these designer drugs have been banned but new analogs are rapidly developed to bypass restrictions. Synthetic cannabinoids are, in general, inexpensive to make.
Many cannabis users are concerned about drug testing requirements for work, school…, and they may unfortunately start using designer drugs to avoid consequences of a positive marijuana test. Standard drug screening tests look for marijuana, designer drugs will not test positive for marijuana. The biggest concern with designer drugs is that they are extremely powerful and can be very dangerous. These drugs frequently cause unpleasant effects and they can be highly addictive with serious withdrawal symptoms. Worse, yet, fatal overdoses with designer drugs have been reported.
Cannabinoid Blockers
Rimonabant was developed by Sanofi-Aventis as an anti-obesity drug that was first approved in Europe in 2006. Rimonabant works by blocking the effects of cannabinoids on the CB1 receptor. Unfortunately, many patients using Rimonabant suffered severe side effects, including depression, suicidal ideation, gastroenteritis, anxiety, irritability, insomnia and other sleep disorders, hot flushes, diarrhea, vomiting, dry or itchy skin, tendonitis, muscle cramps and spasms, fatigue, flu-like symptoms, and increased risk of falling. Rimonabant was withdrawn worldwide in 2008 due to serious psychiatric side effects.
Other Modulators of the Endocannabinoid System (ECS)
There are many, many drugs in the pipeline of the pharmaceutical companies based on the emerging science of the endocannabinoid system (ECS). An endocannabinoid enhancer (eCBE) is a type of drug that enhances the activity of the endocannabinoid system by increasing the concentrations of endocannabinoids in the ECS receptors.
One particular class of eCBE is endocannabinoid reuptake inhibitors (eCBRIs), also called cannabinoid reuptake inhibitors (CBRIs). The inhibition of endocannabinoid reuptake raises the amount of those neurotransmitters available in the synaptic cleft and therefore increases neurotransmission. Examples of different types of eCBEs include fatty acid amide hydrolase (FAAH) inhibitors, monoacylglycerol lipase (MAGL) inhibitors, and endocannabinoid transporter(eCBT) inhibitors.
The aforementioned drugs can be extremely powerful and have profound effects on your endocannabinoid system. There is also the possibility of combining various types of these drugs to create even more focused and powerful effects.
How do the Synthetic ECS Drugs Compare to Old Fashioned Cannabis?
Natural sources of cannabis have been used safely for over a thousand years. Furthermore, there has never been a single death attributed to cannabis use in recorded history.
Do we really need these fancy, new ECS analogs and ECS modulating drugs? Are they safer than cannabis? Are they more effective than cannabis? The new synthetic agents are definitely more expensive than cannabis, a plant that grows so easily in various climates that it has been nicknamed “weed”.
Ready to Take Control of Your Health?
If you’re ready to prioritize your health and are seeking effective, metabolically directed treatments, contact us online or call (732) 268-7663 for a consultation with Dr. Rothman.
Have You Read The Medical Marijuana Series by Dr. Michael Rothman?
In the corresponding blogs of this series, we discuss the role of cannabis, cannabinoids, and the endocannabinoid system in the treatment of chronic pain, anxiety disorders, cancer, multiple sclerosis, and Crohn’s Disease.
- Introduction of Cannabis and its History of Use in Medicine
- The Role of Cannabis, Cannabinoids and the Endocannabinoid System in the Treatment of Chronic Pain
- The Role of Cannabis, Cannabinoids and the Endocannabinoid System in Disorders of your Immune System – such as Cancer and Autoimmune Diseases
- The Role of Cannabis, Cannabinoids and the Endocannabinoid System in Anxiety Disorders
- Pharmaceutically derived Cannabis Extracts Now FDA Approved – Good News or Bad News for Medical Marijuana Patients?
- Pharmaceutical Agents that Affect the Endocannabinoid System, Better than Natural Cannabis?
A full list of references can be found here.
If you’d like to learn more about the benefits of medical marijuana or if you’d like to enroll in the New Jersey Medical Marijuana Program, schedule a consultation by calling (732) 268-7663 or request an appointment online.
