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COWEN COLLABORATIVE INSIGHTS February 25, 2019 Synthetic Cannabis (Schenkel) 2 The Broad Spectrum Of Cannabinoids Cannabinoids fall into three main types: (1) endogenous cannabinoids, which are produced naturally in the bodies of humans and animals; (2) phytocannabinoids, which are isolated from plants; and (3) synthetic cannabinoids, which are produced in the laboratory and may have some structural deviations from the naturally occurring molecules. Of the three types, phytocannabinoids have garnered a lot of interest because of their therapeutic and recreational potential. For example, Marinol and Syndros, which the FDA cleared for the treatment of anorexia associated with weight loss in AIDS patients, include the active ingredient dronabinol, a synthetic delta-9- tetrahydrocannabinol (THC) which is considered the psychoactive component of marijuana. In June 2018, the FDA approved an oral formulation of cannabidiol (CBD), Epidiolex, which GW Pharmaceuticals PLC developed for the treatment of seizures associated with two rare and severe forms of epilepsy in children. n addition to THC and CBD, more than 100 other phytocannabinoids have been identified from the cannabis plant. This includes lesser-known compounds such as tetrahydrocannabivarin (THCV), cannabigerol (CBG), and cannabichromene (CBC). The broad spectrum of phytocannabinoids can bind to a range of different receptors in the human body and induce a wide variety of pharmacological responses. However, due to the limited research into these varying effects, a full understanding of the role of each cannabinoid compound is still poorly understood. With that said, some of the most studied roles are listed in the table below. Figure 9 Approved & Potential Medicinal Roles Of Selected Phytocannabinoids Cannabinoid Percent Of Total Role Cannabinoid Content Tetrahydrocannabinol 15-35% e — Psychotropic (THC) e FDA-approved as appetite stimulant for people with AIDS and antiemetic for people receiving chemotherapy e —_ Alleviates neuropathic pain, spasticity, overactive bladder, and other symptoms Cannabidiol 41-12% e FDA-approved for treating rare seizure disorders (CBD) e — Chronic pain treatment e —_ Being studied for treatment of anxiety, post-traumatic stress disorder, pain, schizophrenia, Parkinson’s disorder and Huntington’s disorder Tetrahydrocannabivarin | <1% e —_ Potential anxiety relief (THCV) e Potential appetite suppressant Cannabigerol <1% e —_ Potential anti-inflammatory (CBG) e —_- Potential anti-cancer Cannabichromene <1% e —_ Potential anti-inflammatory (CBC) e —_- Potential anti-cancer e —_- Potential GI motility modulator Source: Cowen and Company COWEN.COM 17 HOUSE_OVERSIGHT_024833