Introduction to Cannabis.pdf

Introduction to Cannabis Stephan C. Jahn, Ph.D. Pharmacology and Therapeutics University of Florida  Cannabis Cannabis sativa Cannabis indica Cannabis ruderalis Hemp...

Introduction to Cannabis Stephan C. Jahn, Ph.D. Pharmacology and Therapeutics University of Florida  Cannabis Cannabis sativa Cannabis indica Cannabis ruderalis Hemp Marijuana Hashish Cannabidiol Tetrahydrocannabinol (CBD) (THC) History  Use of Cannabis fibers dates back to roughly 8,000 BC  Known to be used in China, India, Egypt, and Mesopotamia  First recorded medical use was in China ~5,000 years ago  First recreational use also in China  Cannabis appears in Hindu holy books  Bhang is consumed at weddings and festivals  In early 1900’s cannabis was considered “an integral part of the culture and religion of the country.”  Introduced into Western medicine in the 1800s  Phased out in 1900s as purified medicines took hold Control of Cannabis  1961 Single Convention on Narcotic Drugs  Included cannabis with opium and others  Prohibited production and supply other than for medical purposes  1971 Convention on Psychotropic Substances  Generated the current “schedule” drugs  Placed THC in Schedule I  Other cannabinoids (i.e. CBD) were not regulated  U.S., among others, broadened regulations  CBD from marijuana is Schedule I  CBD from hemp is legal after 2018 farms bill Chemical Makeup of Cannabis  Over 100 cannabinoids  THC responsible for nearly all psychoactive effects  Absent in roots and seeds  Present at low levels in stems  Present in leaves (2-3%)  High in flowers (up to 25%)  Other compounds can modulate THC effects  Cannabinoid content varies between strains  1960’s marijuana was 2-5% THC  Current street marijuana is 12% THC Cannabinoids  11 types of cannabinoids  Δ9-THC and CBD are two  Δ9-THC (tetrahydrocannabinol)  Only psychoactive cannabinoid  Δ9-THC-acid is not psychoactive  Converted to Δ9-THC during heating or combustion  CBD (cannabidiol)  Produces many of the same effects as THC, but not psychoactive  Reduces psychoactive properties of THC  Concentration in street marijuana has dropped to near 0  CBD-acid is converted to CBD during combustion  100-1,000x more potent than CBD as antiemetic  Historically, all NIH supplied marijuana has been low THC, high CBD Administration  Smoking  Vaporizing  Reduces toxin formation  Eating  Oral tinctures  Topical Absorption  Smoking  Most common  Bioavailability ~25%, but highly variable  THC plasma Cmax in 6-10 minutes  60% after 15 minutes  20% after 30 minutes  Oral (Edibles or THC pill)  Bioavailability ~6%  Higher when in oils  THC plasma Cmax in 2-6 hours Distribution  THC is highly lipophilic  Quickly sequestered by organs with high blood flow  THC can be measured in the blood of chronic users more than a month after cessation Metabolism  Extensive metabolism in liver  Primarily Cytochrome P450s  Three primary metabolites  11-OH-THC  Psychoactive  THC-COOH and glucuronide conjugates  Inactive  High inter-individual variability  Not sex-dependent  CYP2C9 variants reduce clearance Excretion  Eliminated primarily as metabolites  65% in feces  25% in urine  10-20% remaining after 5 days  One low THC marijuana cigarette detectable for up to 2-5 days  Weeks for chronic user Tolerance  Tolerance is seen with long-term use  Receptor desensitization  Receptor downregulation  Some receptors affected more than others  Some effects show tolerance while others don’t Dosing  Dosing is individualized  Inhalation allows dose titration  Dose until desired effects are achieved  10-20 minutes between puffs  Edibles do not  Leads to over-consumption  3 hours between bites  Average 10-20 g per week for medical use  6-7x daily inhalation  2x daily edibles  Low risk of life-threatening overdose  Low concentration of receptors in life-critical brain areas (i.e. respiratory/cardiac centers)  No known instances  Psychotic adverse effects more common (i.e. anxiety)