Document text
Principal Investigator: Thomas F Gamage
Organization: UPSTATE MEDICAL UNIVERSITY
Fiscal Year: 2024
Award: $430,630
Funding agency: National Center for Complementary and Integrative Health
PROJECT SUMMARY
Throughout recorded history, humans have used natural products for medicinal purposes. With the onset of
modern analytical and pharmaceutical methods, the active ingredients in some of these “natural remedies” were
identified and became foundational chemicals in drug development efforts. Among the numerous examples,
aspirin (bark of the willow tree), capsaicin (chili peppers), and opioids (opium poppy plant) are notable for their
analgesic properties. Similar to these other natural products, Cannabis sativa has long been used for medicinal
purposes, including pain relief. The cannabis plant (Cannabis sativa/indica) contains over 100
phytocannabinoids as well as over 500 other identified chemicals, including the terpenoids that give cannabis its
distinctive flavoring and aroma. Beyond 9-THC and CBD, however, difficulties in identifying, isolating and
purifying minor phytocannabinoids in quantities sufficient for in vivo evaluation have hampered adequate
investigation of potential therapeutic uses of individual phytocannabinoids. Recently, we have secured access
to purified minor cannabinoids synthesized via a patented biosynthetic process in quantities that allow for
preclinical in vivo testing. The goal of the proposed project is to provide a comprehensive evaluation of these
compounds alone, and in planned combinations, to determine their potential efficacy as analgesics. In addition,
we will conduct a parallel investigation of selected terpenes that have been identified in the cannabis plant. Novel
analgesic strategies are needed to combat over-reliance on opioids and the resulting secondary consequences
of dependence and morbidity/mortality.
Terms: <9-ene-Tetrahydrocannabinol><Absence of pain sensation><Absence of sensibility to pain><Acetic Acids><Acetylsalicylic Acid><Acids><Acute Pain><Adverse effects><Analgesia Tests><Analgesic Agents><Analgesic Drugs><Analgesic Preparation><Analgesics><Animal Model><Animal Models and Related Studies><Anochlesia><Anodynes><Antinociceptive Agents><Antinociceptive Drugs><Aspirin><Assay><Autonomic pain><Behavior><Bioassay><Biological Assay><Breeding><C sativa><C. sativa><CB1><CB1 Receptor><CB1R><CB2><CB2 Receptor><CB2R><CNR1 gene><CNR2><CNR2 gene><Calcium Channel><Calcium Channel Antagonist Receptor><Calcium Channel Blocker Receptors><Calcium Ion Channels><Cannabidiol><Cannabinoid Receptor CB1><Cannabinoid Receptor CB2><Cannabinoids><Cannabis><Cannabis sativa><Cannabis sativa plant><Capsaicin><Catalepsy><Cell Communication and Signaling><Cell Signaling><Characteristics><Chemicals><Chili Pepper><Closure by Ligation><D9-tetrahydrocannabinol><Delta-9-Tetrahydrocannabinol><Dependence><Development><Dose><Drugs><ELISA><Enzyme-Linked Immunosorbent Assay><Evaluation><Feels no pain><Flavorant><Flavoring><Flavoring Agents><G-Proteins><GTP-Binding Proteins><GTP-Regulatory Proteins><Goals><Guanine Nucleotide Coupling Protein><Guanine Nucleotide Regulatory Proteins><History><Human><Hypothermia><In vivo analysis><Individual><Inflammation><Injections><Intermediary Metabolism><Intracellular Communication and Signaling><Investigation><Legal patent><Ligation><Locomotor Activity><Mediating><Mediation><Medication><Medicine><Metabolic Pathway><Metabolic Processes><Metabolism><Methods><Mice><Mice Mammals><Minor><Modeling><Modern Man><Modernization><Morbidity><Morbidity - disease rate><Motor Activity><Murine><Mus><Natural Products><Natural Remedy><Negotiating><Negotiation><No sensitivity to pain><Nociception Tests><Opiates><Opioid><Opium><Orphan><Pain><Pain Assessment><Pain Measurement><Pain measure><Painful><Papaver><Patents><Peripheral><Pharmaceutical Agent><Pharmaceutical Preparations><Pharmaceuticals><Pharmacologic Substance><Pharmacological Substance><Plants><Poppy><Procedures><Process><Property><Receptor Activation><Receptor Protein><Recording of previous events><Recreation><Rodent><Rodentia><Rodents Mammals><Salix><Secure><Signal Transduction><Signal Transduction Systems><Signaling><Stretching><TRP channel><Tail><Terpene Compound><Terpenes><Terpenoids><Testing><Tetrahydrocannabinol><Therapeutic Effect><Therapeutic Uses><Transient receptor potential channel><Treatment Efficacy><Trees><Urine><VDCC><Visceral pain><Voltage-Dependent Calcium Channels><Willow><abuse liability><abuse potential><analgesia><antinociception><antinociceptive><biological signal transduction><cannabimimetics><cannabinoid receptor 1><cannabinoid receptor 2><cannabinoid receptor type 1><cannabinoid receptor type 2><cannabinoid type 1><combat><cytokine><delta(1)-THC><delta(1)-Tetrahydrocannabinol><delta(9)-THC><delta(9)-Tetrahydrocannabinol><determine efficacy><developmental><drug development><drug discrimination><drug/agent><efficacy analysis><efficacy assessment><efficacy determination><efficacy evaluation><efficacy examination><enzyme linked immunoassay><evaluate efficacy><examine efficacy><experiment><experimental research><experimental study><experiments><histories><in vivo evaluation><in vivo testing><inflammatory pain><intervention efficacy><model of animal><mortality><mouse model><mu opioid receptors><murine model><natural hypothermia><naturally occurring product><neuropathic pain><non-narcotic analgesic><non-opiate analgesic><non-opioid><non-opioid analgesic><non-opioid therapeutics><nonnarcotic analgesics><nonopiate analgesic><nonopioid><nonopioid analgesics><novel><pain assay><pain behavior><pain killer><pain medication><pain patient><pain perception><pain relief><pain reliever><pain sensation><painful neuropathy><painful sensation><painkiller><pharmaceutical><phytocannabinoid><pre-clinical><pre-clinical evaluation><preclinical><preclinical evaluation><receptor><receptor binding><receptor bound><relieve pain><sciatic nerve><screening><screenings><therapeutic efficacy><therapy efficacy><urinary><Δ(1)-THC><Δ(1)-tetrahydrocannabinol><Δ(9)-THC><Δ(9)-tetrahydrocannabinol><Δ-9-tetrahydrocannabinol><Δ9-tetrahydrocannabinol><μ opioid receptors><μ-OR><μOR>