The Nuero-Science & Toxicology of Marijuana
Louisiana Association of Drug Court Professionals
Lafayette, Louisiana
June 26, 2015
Judge Mary A. Celeste (Ret.)
The following presentation may not be copied
in whole or in part without the written permission of the author
© Celeste
Overview
Legal History of MJ
Neuro-Science THC/Cannabis
Science/Medical Marijuana
THC Toxicology
Role of the Toxicologist
Early History
Early MJ History
3000 B.C. Siberia burial grounds
3000 B.C. Chinese as Medicine
Regulations and restrictions on the sale as a drug began as early as 1619
U.S. Washington Hemp in Mt Vernon.
1910-20 USA
Marijuana as a Poison
1910 there was a wave of legislation aimed to strengthen requirements for sale
Legislation restricted all narcotics, including cannabis, as poisons, limit their sale to pharmacies, and required doctor's prescriptions.
Under poison laws definitions had to labeled as poison
Outright prohibitions began in the 1920s
1930s Cannabis as a Pharmaceutical
Parker-Davis and Eli Lily were selling standardized extracts of marijuana for use as an analgesic, an antispasmodic and sedative.
Another manufacturer, Grimault & Company, marketed marijuana cigarettes as a remedy for asthma
1930-40’S
1950s-1970 USA
Boggs Act 1952
Narcotics Control Act (NCA)1956.
NCA made a first-time possession offense a minimum of two to ten years with a fine up to $20,000.
1969 Leary v. U.S. decision the U.S. Supreme Court held the Marijuana Tax Act to be unconstitutional, since it violated the 5th Amendment privilege against self-incrimination.
1950s-1970 USA
In response, Congress passed the Control Substances Act as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970, which repealed the Marijuana Tax Act
Cannabis became a Schedule I Control Substance with the creation of the Control Substances Act. 1970 along with heroine and LSD
On December 1, 1975, the Supreme Court ruled that it was "not cruel or unusual for Ohio to sentence someone to 20 years for having or selling cannabis
Control Substances Act
A controlled (scheduled) drug is one whose use and distribution is tightly controlled because of its abuse potential or risk.
Five categories for drugs Schedule I is reserved for what the DEA considers to be the "most dangerous" drugs without currently accepted medical value.
Control Substances I-V
Schedule I — drugs with a high abuse risk. These drugs have NO safe, accepted medical use in the United States. Some examples are heroin, marijuana, LSD, PCP, and crack cocaine.
Schedule II — drugs with a high abuse risk, but also have safe and accepted medical uses in the United States. These drugs can cause severe psychological or physical dependence. Schedule II drugs include certain narcotic, stimulant, and depressant drugs. Some examples are morphine, cocaine, oxycodone (Percodan®), methylphenidate (Ritalin®), and dextroamphetamine (Dexedrine®).
Schedule III, IV, or V — drugs with an abuse risk less than Schedule II. These drugs also have safe and accepted medical uses in the United States. Schedule III, IV, or V drugs include those containing smaller amounts of certain narcotic and non-narcotic drugs, anti-anxiety drugs, tranquilizers, sedatives, stimulants, and non-narcotic analgesics. Some examples are acetaminophen with codeine (Tylenol® No.3), paregoric, diazepam (Valium®), alprazolam (Xanax®), propoxyphene (Darvon®), and pentazocine (Talwin®).
2015 Schweder Challenges Schedule I Classification
Defense attorneys argued it's impossible to say marijuana has no accepted medical value, and that the federal classification of the plant is unconstitutional for several reasons:
23 states have legalized marijuana for medical purposes;
A growing body of research exists highlighting marijuana's medical promise;
Federal view of marijuana is evolving,
Judge Upholds Federal Government's Classification That Marijuana Is 'Dangerous'
United States v. Bryan R. Schweder, et al., judge in California on Wednesday denied a motion from a group of nine defendants charged with growing marijuana who were contending the federal government's classification marijuana of as one of the "most dangerous" substances is unconstitutional.
June 2, 2015 Eastern District California Court Denies Motion to Reconsider in Schweder Marijuana Case
Marijuana History 1990-2005
1996 California is the first State to decriminalize medical marijuana
2005 U.S. Supreme Court rules in U.S. v. Oakland Cannabis Buyers’ Cooperative and Gonzales v. Raich that the federal government has a right to regulate and criminalize cannabis, even for medical purposes
Congressional MJ Bills
Carers Act
March 2015 Carers Act (The Compassionate Access, Research Expansion and Respect States) first-ever bill in the U.S. Senate to legalize MMJ.
Bipartisan group of senators reclassify MJ as a Schedule II controlled substance.
If passed, the legislation would remove any potential of federal prosecution for individuals using marijuana for medical purposes.
Would allow marijuana to be prescribed for veterans receiving care in VA facilities.
Congressional MJ Bills
May 21, 2015 Allowing VA doctors to recommend MMJ to their patients in states where MMJ is legal.
To amend the Controlled Substances Act to provide that Federal law shall not preempt State law.
To decriminalize MJ at the Federal level
To amend the Internal Revenue Code for the taxation of MJ
Nuero-Science
Marijuana/Cannabis
Cannabis
Flowering plants that include three putative varieties, sativa, indica, and ruderalis. Indigenous to Central and South Asia
Most used illicit drug in the world
Active ingredient Delta 9 THC. Resinous substance is known as Hashish.
MJ & Its Compounds
(aka molecules)
483 chemical constituents isolated and identified in cannabis to date
About 85 cannabinoids. Some are psychoactive and some are not.
THC main psychoactive cannabinoid
Some 20 Flavonoids
120 Terpenes
The Human Body Systems
The Endocannabinoid System
Endocannabinoids
Endocannabinoids are in every living animal on the planet above Hydra and Mollusks, with the exception of insects
UNTIL 2014 when it was found in a fruit fly.
Endocannabinoids are the substances our bodies naturally make to stimulate cannabinoid receptors.
Cannabinoid Receptors
in Brain & Body
Cannabinoid receptors are present throughout the body, embedded in cell membranes, and are believed to be more numerous than any other receptor system.
What are Receptors
Receptors are binding sites for chemicals in the brain, chemicals that instruct brain cells to start, stop or otherwise regulate various brain and body functions.
The chemicals which trigger receptors are known as neurotransmitters.
Receptors in Brain & Body
The sensations of slight euphoria, relaxation, and amplified auditory and visual perceptions produced by marijuana are due almost entirely to its effect on the cannabinoid receptors in the brain.
Brain Receptors for Cannabis
There are currently two known subtypes of cannabinoid receptors CB1andCB2
The CB1receptor is expressed mainly in thebrain (central nervous system or CNS). Also in thelungs, liver and kidneys
Brain Receptors for Cannabis
The CB2receptor is expressed mainly in theimmune system and inHMS (hema to(e) pi etic) cells the blood cells that give rise to all other blood cells. They are located in the bone marrow
CB2 receptors have been recently discovered in the central nervous system, the microglial cells and they seem to be in certain neurons as well.
However, it remains a quite controversial and debated issue.
Brain Receptors for Cannabis
Mounting evidence suggests that there are novel cannabinoid receptors that is, non-CB1and non-CB2, expressed inendothelialcells the thin layer of simplesquamous cellsthat lines the interior surface ofblood and lymphatic vessels.
Location of Cannabinoid Recepters
Two cell receptors
Cannabinoid Receptors
1992 Discovered natural transmitter or “endocannabinoid” that fits those receptors: anandamide.
More recently an even more important endocannabinoid that normally activates these receptors was discovered 2AG (2 arachido noyl glycerol)
Researchers have developed compounds to both stimulate or block CB receptors to study how they function.
Anandamide
The Bliss Molecule
THC begins this process by binding to the CB1 receptors for anandamide.
Anandamide is involved in regulating mood, memory, appetite, pain, cognition, and emotions.
Anandamide
Has been found to fight against human breast cancer
Three compounds that strongly resemble anandamide were found in dark chocolate 1996
Scheme of the endocannabinoid system
The Endocannabinoid System
Corollary
Morphine and endorphins
Opiate Receptors
In 1972 brain researchers from Johns Hopkins University found that the human brain's neurons had specific receptor sites for opiate drugs: opium, heroin, codeine and morphine.
The active ingredient in all these opiates - morphine - had a chemical structure similar to endorphins, a class of chemicals present in the brain .
Endorphins are feel-good chemicals naturally-manufactured in the brain when the body experiences pain or stress. They are called the natural opiates of the body.
How brain cells communicate
Brain cells (neurons) communicate with each other and with the rest of the body by sending chemical “messages.”
These messages help coordinate and regulate everything we feel, think, and do.
How brain cells communicate
Typically, the chemicals (called neurotransmitters) are released from a neuron (a presynaptic cell), travel across a small gap (the synapse), and then attach to specific receptors located on a nearby neuron (postsynaptic cell).
This spurs the receiving neuron into action, triggering a set of events that allows the message to be passed along.
Cell Communication
Cannabinoids Receptors
Work Differently From Other Neurotransmitters
The cannabinoid receptor is a new class of receptor is indicated primarily by the finding that its amino acid sequence differs significantly from that of any other known type of receptor
Cannabinoids Receptors
Work Differently From Other Neurotransmitters
EC system communicates its messages in a different way because it works “backward.”
When the postsynaptic neuron is activated, cannabinoids (chemical messengers of the EC system) are made “on demand” from lipid precursors (fat cells) already present in the neuron.
Then they are released from that cell and travel backward to the presynaptic neuron, where they attach to cannabinoid receptors.
Cell Communication
why is this important?
Since cannabinoids act on presynaptic cells, they can control what happens next when these cells are activated.
In general, cannabinoids function like a “dimmer switch” for presynaptic neurons, limiting the amount of neurotransmitter that gets released
Cannabinoid Receptors & Dopamine
Brain microdialysis has proven that opiates, cocaine, amphetamines, nicotine and alcohol all affect dopamine production, whereas marijuana does not.
Is mj Physically Addictive ?
yes… AT A Reduced Risk
Marijuana is distinguished from most other illicit drugs by the locations of its brain-receptor sites for two predominant reasons:
The lack of receptors in the medulla significantly reduces the possibility of accidental, or even deliberate (No) death from THC
The lack of receptors in the meso cortico limbic pathway significantly reduces the risks of addiction and serious physical dependence
Is mj Addictive?
Yes Psychologically
Psychology Today: “Addicted to something is more than simply being physically dependent on a drug and experiencing physiological effects if the drug is stopped suddenly.”(withdrawal)
“Addiction” refers to behaviors that are compulsive, partially out of control or worse, and often escalating in severity and intensity”
cannabinoid Use Begets
More endocannabinoids
begets more Cannabinoid Receptors
Research has shown that small doses of cannabinoids from cannabis can signal the body to make more endocannabinoids and build more cannabinoid receptors.
This is why many first-time cannabis users don't feel an effect, but by their second or third time using the herb they have built more cannabinoid receptors and are ready to respond.
chronic Use and tolerance reduces receptors
An alternative hypothesis about how dynamic tolerance to marijuana operates involves receptor "down-regulation," in which the body adjusts to chronic exposure to a drug by reducing the number of receptor sites available for binding
Other Molecules/Compounds In MJ
flavonoids terpenes Terpenoids
Compounds that produce flavor and fragrance in plants
Some 20 Flavonoids
120 Terpenes
Falvanoids
Some Flavonoids are cannabinoids
Psychoactive themselves, or are able to modulate or potentiate the affect of the psychoactive cannabinoids
Does beer have anthing
in common with MJ
Terpenoids
Terpenoids are found in many plants
Most common Terpenoid is
Beta-myrcene found in bay leaves, hops lemongrass
Flavanoids
Types of flavonoids in the Cannabis plant
(cannflavine A, B and C,vitexin, isovitexin, apigenin, kaempferol, quercetin, luteolin and orientin).
The total content of flavonoids in the Cannabis' leaves and flowers can reach 2.5% of its dry weight
In broccoli, green tea, grapefruit, pomegranate
Other Phytocannabinoids
Plant that have been shown to interact directly with cannabinoid (CB) receptors i.e. Echinacea spp
Plants that have been found to contain non-psychoactive cannabinoids i.e. echinacea purpura
Plant that have been suggested to exert cannabinoid effects but do not interact directly with cannabinoid (CB) receptors i.e. Salvia divinorum
Science/Medical Marijuana
Plants to Medicine Quiz
MMJ & THC Derivatives
5 trials of medical cannabinoids have been conducted. Results have shown effectiveness in reducing pain from neuropathy, diabetes and fibromyalgia.
The FDA has approved two cannabinoid medications, dronabinal (marinol) and nabilone (cesamet).
Prescribed for controlling nausea and vomiting caused by chemotherapy and to treat anorexia in HIV patients.
Other cannabinoid-based medications are under FDA review for treating cancer pain and other conditions.
MMJ & THC Derivatives
Sativex (clinical phases)
Marinol (FDA approved)
Cesamet (FDA approved)
Ebideolex/cannabidoil/CBD (orphan drug status)
Sativex
Available in the United Kingdom and Canada
Chemically pure mixture of plant-derived THC and Cannabidiol Formulated as a mouth spray
Relieves cancer-associated pain, spasticity and neuropathic pain in multiple sclerosis
2 Major cannabinoids
CBD Cannabidiol-Sativex
(anti-convulsive, anti-arthritic)
nonpsychoative
CBN Cannabinol-Mildly psychoactive, CBN is thought to act as a weak agonist of both the CB1 and CB2 receptors,
(anti-epileptic)
the Most Disregarded cannabinoid
Cannabic-chromene CBC –(anti-inflamatory)
the “stem cell” of cannabinoids. It is the precursor to THC, CBD, and CBC. “THCA” psychoactive
This could be a result of its interaction with anandamide
CBC inhibits the uptake of anandamide, which allows it to stay in the bloodstream longer.
Cannabinoids & Brain cancer
Dr. Guzman Animal Studies
Rat MRIs
Brain Tumors
1/3 Tumors Shrunk
1/3 Totally Eradicated
1/3 No Results