Synthetic versions of THC and CBD, such as dronabinol and Epidiolex, are perfectly healthy and safe synthetic cannabinoids. These syntheses are exact copies of THC and CBD, and so behave in the same way when binding to CB1 and CB2 receptors. They are not chemically identical to other, much more dangerous synthetic cannabinoids, such as K2 and Spice, who are only considered synthetic cannabinoids due to their ability to activate CB1 and CB2 receptors; they are very chemically different from the cannabinoids found in cannabis.
Many were synthesized in the late 90s and into the 2010s from laboratories around the world. Among some of the more prominent names, John W. Huffman of Clemson University synthesized over 450 cannabinoids in the JWH series, Alexandros Makriyannis of the Department of Medicinal Chemistry at Northeastern University who synthesized nearly 50 in the AM series and Raphael Mechoulam and his team at Hebrew University who synthesized a handful in the HU series.
Ajulemic acid (AB-III-56, HU-239, IP-751, CPL7075, CT-3, anabasum) is a psychoactive, non-psychotropic synthetic cannabinoid that binds primarily to CB2 receptors, though its true method of action has not yet been confirmed. Extremely chemically similar to THC, it’s been shown to produce pain relieving and anti-inflammatory effects in a few clinical trials, without THC’s signature high. As of 2005, it’s slowly being developed for the treatment of arthritis. Minor side effects include dry mouth, tiredness and dizziness. In doses of 40 mg or more in animal models, it showed slight psychotropic properties, but still negligible compared to THC.
Dronabinol (Marinol, levonantradol, syndros, CP50556-1) is a psychoactive psychotropic synthetic cannabinoid that binds to both CB1 and CB2 receptors and is chemically based on THC. It was first created in 1985 after the AIDS epidemic saw widespread use of medicinal marijuana to address appetite stimulation, pain relief and depression. The FDA approved the synthetic cannabinoid the same year under the name Marinol. Currently available as an oral capsule, dronabinol in particular has been shown to assist with anorexia, cachexia, bulimia, cancer, HIV / AIDS, insomnia, sleep apnea, Alzheimer’s disease, dementia and nausea. Side effects include general weakness, heart palpitations, tachycardia or an increased heart rate and a very small chance of nausea, abdominal pain, dizziness and similar temporary symptoms associated with small THC doses.
Epidiolex is a psychoactive non-psychotropic synthetic cannabinoid based off of CBD developed by GW Pharmaceuticals. It is chemically identical to CBD, and was created for the treatment of childhood epilepsy in two specific disorders, Lennox-Gastaut syndrome and Dravet syndrome. Epidiolex was the first pharmaceutical cannabinoid-based medicine to be approved by the US FDA after CBD was removed from marijuana’s Schedule I and placed in Schedule V in June of 2018, though this came before CBD was removed from the scheduling entirely and fully legalized federally.
Nabilone (Cesamet) is a psychoactive, psychotropic synthetic cannabinoid that is chemically based on and nearly identical to THC. Like THC, it binds primarily to CB1 receptors, and is an FDA-approved treatment for the nausea associated with chemotherapy. Nabilone in particular has been shown to assist with diabetes, HIV / AIDS, nausea, seizures, epilepsy, spasticity, multiple sclerosis and fibromyalgia. Typically taken in 8 mg doses, nabilone has been shown to be more effective than carboplatin. It was originally developed in 1985 by Eli Lilly and Company, but was purchased by Valeant Pharmaceuticals in 2004, who succeeded in getting it approved in the US in 2006, and later in Europe in 2007.
Nabiximol (Sativex, Cannador, GW-1000, N02BG10, SAB378) is a psychoactive psychotropic synthetic cannabinoid-based medicine developed by GW Pharmaceuticals in the early 2000s. It utilizes synthetic cannabinoids chemically identical to THC and CBD in a 1:1 ratio, most often administered in the form of a sublingual spray. A 2009 meta-analysis and a 2014 systematic review both found nabiximol to be moderately effective at treating spasticity, pain and urinary dysfunction, contrary to the increasingly prevalent effectiveness of the natural THC and CBD varieties. Nabiximol was approved by Health Canada in 2005 to treat neuropathic pain and MS, and further approved in 2007 for the treatment of cancer related pain. Despite being developed in the UK, it wasn’t approved for prescription there until 2010.
ST-403 is a psychoactive, non-psychotropic synthetic cannabinoid compound synthesized by the University of Washington Bioengineering made specifically to kill cancer cells. UW BioEng has licensed production, use and sale of the product to Pascal Biosciences, a Canadian drug development company. ST-403 is an altered THC molecule that does not activate cannabinoid receptors and is over 300 times more effective at killing cancer cells than THC is. It works by disrupting the formation of microtubules during mitosis, preventing cancer cell replication and triggering cell death. The National Cancer Institute’s tests using the compound concluded that “the molecules do not work like anything else we’ve tried before, and we’ve tried millions of compounds.” ST-403 is expected to make additional progress in becoming commercially available in early 2019.
Other Safe Synthetic Cannabinoids
Aside from the more common ones named above, other safe synthetic cannabinoids include AM251, CP55940, HU-320, HU-345, HU-336, HU-444, JWH-015, JWH-133, LBP-1, SR141716, SR144528, NESS0327, NESS040C5, O-1057 and O-1812.
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