Steven G. Kinsey, PhD Associate Professor, Department of Psychology West Virginia University sgkinsey@mail.wvu.edu
Any opinions expressed are my own and do not reflect any official position of WVU beanpot.co
Cannabinoids are cannabis-like compounds Plant-derived Marijuana, hashish, THC Synthetic Spice, K2, Buzz Endogenous i.e., endocannabinoids Naturally produced in the body solutions-recovery.com
Chemical classes Cannabinoids (100+) Nitrogenous cmpds (27) Amino acids(18) Proteins/ enzymes (11) Sugars (34) Hydrocarbons (50) Simple alcohols (7) Simple aldehydes (12) Simple ketones (13) Simple acids (21) Fatty acids (22) Simple esters/lactones (13) Steroids (11) Terpenes (20) Non-cannabinoid phenols (25) Flavoroids (21) Vitamins (1) Pigments (2) Elements (9) ------------------------------------- Total known compounds (483) O O H THC http://forum.grasscity.com/toking-tools/402939-$$blunt-joint$$-smokin-picture-thread-5.html
Medical use in China Religious use in India Hashish use in Arab world Western world learns of bioactivity Marijuana Tax Act Medical use legalized in CA & AZ Synthetics banned by DEA Rec. use legalized in WA & CO 2700 BCE 2000 BCE 1000 1850 s 1937 1964 1996 2013 9 -THC discovered (Israel) CB receptor cloned Endocannabinoids discovered
The high Mild euphoria and relaxation Perceptual alterations Time distortion Impaired cognition - memory recall Altered motor function - complex tasks http://reason.com/assets/mc/mwelch/2010_09/snoop_dogg_stoned.jpg
Peripheral effects: heart rate appetite, the munchies emesis (vomiting) intraocular pressure http://marijuana.cc/2013/06/25/top-5-indica-strains-in-2013/
heart rate appetite movement pain sensitivity muscle tone Self-administration Memory disruption http://www.finalpuff.co.uk; theragblog.blogspot.com
THC tetrad effects in mice
Red = abundant CB 1 receptor expression Black = moderately abundant CB 1 receptor expression Adapted from Joy JE et al, eds. Marijuana and Medicine. 1999.
Expression of the CB 1 Receptor Gene in Human Tissue Spleen Stomach Ileum Prostate Testis Placenta Uterus Myocardium Skeletal Muscle Liver Lung Kidney Spinal Cord Whole Brain Adipose Engeli S et al. Diabetes. 2005;54:2838-2843. 0 1 2 3 4 5 Relative CB 1 Gene Expression (AU) 12
Presynaptic Neuron CB 1 CB 1 anandamide Postsynaptic Neuron 2-AG
Presynaptic Neuron JWH-018 JWH-018 THC CB 1 JWH-018 THC CB 1 THC Postsynaptic Neuron anandamide 2-AG
harmreductioncenter.blogspot.com
THC withdrawal Cannabis Use Disorder Affects ~2-6% of users 1 Disturbs sleep, GI function, emotionality Treatment Behavior modification No FDA approved pharmaceutical treatment 1. Hasin et al., 2016
Acute cannabis reduces anxiety & depression Withdrawal: Impairs daily activity anxiety, depression cravings Relapse to cannabis use http://marisworld.co.uk/wp-content/uploads/2012/06/woman-anxious.jpg
Trexler et al., in prep
Heavy use = same respiratory problems as tobacco use Tar & CO 3-5x higher than tobacco due to deep inhalation, holding in lungs, unfiltered Safety of edible forms untested
Herbal incense sold since 2002 includes synthetic cannabinoids Legal by state, not detectable by marijuana tests 2011: 11.4% 12 th graders used spice in prior 12 mo 1 1 Monitoring the Future 2011 leadrecoverycenter.com
Psychological: anxiety, psychosis, paranoia Physiological: nausea, hyperventilation, diaphoresis, pallor, seizures, numbness, muscle twitching Aka, Weaponized marijuana Beaconnews.ca
JWH = John W. Huffman Chemist at Clemson I thought it was sort of hilarious at the time then I started hearing about some of the bad results washingtonpost.com
Seely et al., 2013
How can we harness the positive effects of cannabinoids, without their negative side effects? No high = abuse http://marijuana.cc/2013/06/25/top-5-indica-strains-in-2013/
Mix of cannabinoids Approved in Canada for pain: Multiple sclerosis & cancer Side effects: dizziness, fatigue Phase III trials for neuropathic pain in cancer in US
Rimonabant (Acomplia): Significant reductions in body weight! But, suicidal ideation Pulled from market
Increase endocannabinoids Block the enzymes that break them down No need to administer cannabinoids!
Presynaptic Neuron MAGL JZL184 2-AG CB 1 CB 1 URB597 anandamide Postsynaptic Neuron FAAH 2-AG
Increase endocannabinoids Block the enzymes that break them down No need to administer cannabinoids! Target other receptors CB 2 receptors, others(?) Allosteric sites e.g., alcohol, benzodiazepines Do no bind directly to CB 1
Presynaptic Neuron MAGL 2-AG ZCZ011 CB 1 CB 1 ZCZ011 anandamide Postsynaptic Neuron FAAH 2-AG
CB 1 pos allosteric modulation blocks neuropathic pain in mice Ignatowska-Jankowska et al., 2015
Depression Anxiety Eating disorders Arthritis Epilepsy Brain injury/stroke Fibromyalgia Migraine Cancer (Anti-tumor) Tourette s syndrome Neurotrauma/Neurotoxicity Pain Memory enhancement Drug, Alcohol addiction Smoking cessation Spasticity (Multiple Sclerosis, spinal cord injury) Neurodegenerative disorders (ALS, Parkinson s, Alzheimer s)
Depression Anxiety Eating disorders Arthritis Epilepsy Brain injury/stroke Fibromyalgia Migraine Cancer (Anti-tumor) Tourette s syndrome Neurotrauma/Neurotoxicity Pain Memory enhancement Drug, Alcohol addiction Smoking cessation Spasticity (Multiple Sclerosis, spinal cord injury) Neurodegenerative disorders (ALS, Parkinson s, Alzheimer s)
Clinical use of cannabinoids Anti-emesis Chronic wasting Glaucoma intraocular eye pressure Neuropathic pain Epilepsy?
What about cannabidiol? Very little is understood about CBD, a plant-based cannabinoid Does not bind to cannabinoid receptors Seems to have some anti-inflammatory effects in rodents Effects in humans not well studied Keep in mind all plant-based cannabinoids are Schedule I compounds
What about cannabidiol? Either THC or CBD attenuate convulsions in rats CBD may be effective as antiepileptic in kids with Dravet syndrome Only 1 study to date, so replication is needed Again, access to CBD is limited due to Schedule I status
Take-home points Cannabinoids act on CB 1 (behavior) and CB 2 (immune) receptors Endocannabinoids are the natural ligands Enzyme inhibitors that increase ecbs block pain and inflammation in animals, unclear how effective in people Manipulation of different ecb system targets may have cleaner health applications than cannabis