4. www.outco.com
Molecular structure has a huge effect on how
molecules interact with the human body. Small
changes in stereochemistry, functional groups or
carbon backbone will change the effect.
4
Same but Different
5. www.outco.com
Vanilla
• Second most expensive spice
• Worlds favored flavoring
• 95% of all “vanilla” products use synthetic vanillin
• Real vanilla better for cookies, syn. vanillin for baking
5
Same but Different
Real Fake
Plus hundreds of other compounds
6. www.outco.com
Total Synthesis vs. Semisynthesis
• Taxol is an anticancer drug
isolated from Pacific Yew
• First total synthesis by Holton:
46 linear steps
• Semisynthesis by Holton with
80% yield from European Yew
6
Same but Different
8. www.outco.com
• Heroin acts on opioid receptor
• Relieves pain
• Produces feeling of euphoria
• Highly addictive
• High doses can depress breathing
• Naxloxone reverses effects of opioid overdose
• Has stronger affinity for opioid receptor
• Works within 2 minutes of injection
8
The Opioid Epidemic
9. www.outco.com
• Fentanyl is a synthetic opioid, prescribed by doctors
for chronic pain
• Higher potency increases risk of overdose
9
The Opioid Epidemic
11. www.outco.com
• Professor Emeritus, Organic Chemistry, Clemson
University
• Began in 1984 to synthesis novel cannabinoids
• Focused on targeting endocannabinoid receptors
• For multiple sclerosis, HIV, chemoterapy, …
• Over 450 synthetic cannabinoids developed
• First used as marijuana alternatives in Germany in
late 2000s 11
John William Hoffman
12. www.outco.com
• Professor, Department of Medicinal Chemistry,
Northeastern University
• Study of interactions ‘cannabinoid-like’ molecules
with CB1 & CB2 receptor
• Design and synthesis of novel therapeutically useful
drugs for pain, appetite and central nervous system
diseases
12
Alexandros Makriyannis
13. www.outco.com
• Professor, Department of Medicinal Chemistry,
Hebrew University of Jerusalem
• First to isolate, characterize and synthesis of THC
• Isolated and identified endocannabinoids
• HU-210
• Promotes proliferation, but not differentiation, of
hippocampal neural stem and progenitor cells
• Indication of antianxiety and antidepressant effects
• Implicated in inflammation prevention due to amyloid
beta proteins involved in Alzheimer’s
13
Raphael Mechoulam
14. www.outco.com
• Synthesized in the 1970s and 1980s
• Recently discovered in recreational drugs
• CP 55,940
• Widely used cannabinoid research tool
• Neuroprotective by reducing intracellular calcium
release
14
Pfizer
15. www.outco.com
• Molecules that target CB1 & CB2 receptors
• No precedent in scientific literature
• Appear to be rationally designed
• Little to no information about pharmacology and
toxicology
15
Designer Cannabinoids
16. www.outco.com
• Agonist binds to receptor: Key for the lock
• Full: Copy of key
• Partial: Lock Pick
• Inverse: Opposite effect of normal
• Antagonist blocks others from binding: Putty for lock
16
Terms and Conditions
17. www.outco.com
• THC: Partial agonist to CB1 & CB2
• CBD: Antagonist for CB1 & CB2
• 2-AG: Full agonist for CB1
17
Terms and Conditions
18. www.outco.com
• All claims made are ’soft’
• Didn’t find a drug that is FDA approved
• Most studies are in animal models or in vitro
• Therefore not directly applicable to humans
18
Terms and Conditions
20. www.outco.com
• Full CB agonist
• Potent analgesic (painkiller)
• Prevent inflammation caused by amyloid beta proteins
involved in Alzheimer’s disease
• Prevent cognitive impairment, loss of neuronal markers
• Reduces voluntary wheel running in mice
20
WIN 55,212-2
21. www.outco.com
• Potent CB2 agonist
• 200x more selective for CB2 over CB1
• Not psychoactive as CB2 selective
• Prevent inflammation caused by amyloid beta
proteins involved in Alzheimer’s disease
21
JWH-133
22. www.outco.com
• Prof. Bob Moore II, University of Tenesee
• CB2 inverse agonist
• In pre-clinical development for treatment of
neurodegenerative disorders and traumatic brain
injury
22
SMM-189
doi: 10.1002/prp2.159
24. www.outco.com
• Anti-obesity drug / appetite suppressant
• Inverse agonist for CB1
• Approved in 2006 (EU), first of its class
• Withdrawn in 2008
• Risk of serious psychiatric problems
• 10% experience depressive disorders
• 1% suicidal ideation
• Additionally: nausea, upper respiratory tract infections,
anxiety, insomnia, diarrhea, vomiting, …
24
Rimonabant, Sanofi-Aventis
25. www.outco.com
• Full agonist for CB1 & CB2
• Similar effects to THC, but 5x greater
• Death linked to JWH-018 by drug toxicity and organ
failure
25
JWH-018
27. www.outco.com
• “Unnatural” enantionmer of HU-210
• Not a CB agonist
• NMDA antagonist
• Anesthetic effect like ketamine or synthetic opioids
• No cannabis-like effects
• But anticonvulsant and neuroprotective
• Studied for treating head injury, stroke, or cancer
• Currently in Phase I for treating brain cancer
27
Dexanabinol
28. www.outco.com
• Patented by Mark Scialdone, PhD
• He reports similar ‘High’ as THC
• No further clinical study beyond his own consumption
• He hydrogenated cannabis extract, then consumed it
28
Hydrogenated Cannabinoids
